+ Exomiser Analysis Results for + Anonymous +
+ +
+
+
+
+
+
+ Analysis Settings
+Settings used for this analysis:
+---
+sample:
+ genomeAssembly: "hg38"
+ vcf: "/home/ivanwilliamharsono/Downloads/trio_patient/annotated/V350145665_L04_B5EHOMdmhwXAAAA-515-SnpEff-dbSNP-ClinVar-dbNSFP_annotated-deepVariant.vcf.gz"
+ hpoIds:
+ - "HP:0000007"
+ - "HP:0001433"
+ - "HP:0001903"
+ - "HP:0001541"
+ - "HP:0010972"
+ - "HP:0005561"
+ - "HP:0001396"
+ - "HP:0001410"
+ - "HP:0002910"
+ - "HP:0001399"
+ - "HP:0000938"
+ - "HP:0001642"
+ - "HP:0200114"
+ - "HP:0003073"
+ - "HP:0003233"
+ - "HP:0001873"
+ - "HP:0002151"
+ - "HP:0031964"
+ - "HP:0031956"
+ - "HP:0002366"
+ - "HP:0006568"
+ - "HP:0004333"
+ - "HP:0001531"
+ pedigree: {}
+ age: {}
+analysis:
+ inheritanceModes:
+ AUTOSOMAL_RECESSIVE_COMP_HET: 2.0
+ MITOCHONDRIAL: 0.2
+ AUTOSOMAL_RECESSIVE_HOM_ALT: 0.1
+ X_DOMINANT: 0.1
+ AUTOSOMAL_DOMINANT: 0.1
+ X_RECESSIVE_COMP_HET: 2.0
+ X_RECESSIVE_HOM_ALT: 0.1
+ frequencySources:
+ - "THOUSAND_GENOMES"
+ - "TOPMED"
+ - "UK10K"
+ - "ESP_AFRICAN_AMERICAN"
+ - "ESP_EUROPEAN_AMERICAN"
+ - "ESP_ALL"
+ - "EXAC_AFRICAN_INC_AFRICAN_AMERICAN"
+ - "EXAC_AMERICAN"
+ - "EXAC_EAST_ASIAN"
+ - "EXAC_FINNISH"
+ - "EXAC_NON_FINNISH_EUROPEAN"
+ - "EXAC_OTHER"
+ - "EXAC_SOUTH_ASIAN"
+ - "GNOMAD_E_AFR"
+ - "GNOMAD_E_AMR"
+ - "GNOMAD_E_EAS"
+ - "GNOMAD_E_FIN"
+ - "GNOMAD_E_NFE"
+ - "GNOMAD_E_OTH"
+ - "GNOMAD_E_SAS"
+ - "GNOMAD_G_AFR"
+ - "GNOMAD_G_AMR"
+ - "GNOMAD_G_EAS"
+ - "GNOMAD_G_FIN"
+ - "GNOMAD_G_NFE"
+ - "GNOMAD_G_OTH"
+ - "GNOMAD_G_SAS"
+ pathogenicitySources:
+ - "REVEL"
+ - "MVP"
+ steps:
+ - failedVariantFilter: {}
+ - variantEffectFilter:
+ remove:
+ - "CODING_TRANSCRIPT_INTRON_VARIANT"
+ - "FIVE_PRIME_UTR_EXON_VARIANT"
+ - "THREE_PRIME_UTR_EXON_VARIANT"
+ - "FIVE_PRIME_UTR_INTRON_VARIANT"
+ - "THREE_PRIME_UTR_INTRON_VARIANT"
+ - "NON_CODING_TRANSCRIPT_EXON_VARIANT"
+ - "NON_CODING_TRANSCRIPT_INTRON_VARIANT"
+ - "UPSTREAM_GENE_VARIANT"
+ - "DOWNSTREAM_GENE_VARIANT"
+ - "INTERGENIC_VARIANT"
+ - "REGULATORY_REGION_VARIANT"
+ - frequencyFilter:
+ maxFrequency: 2.0
+ - pathogenicityFilter:
+ keepNonPathogenic: true
+ - inheritanceFilter: {}
+ - omimPrioritiser: {}
+ - hiPhivePrioritiser:
+ runParams: "human, mouse, fish, ppi"
+ - phenixPrioritiser: {}
+outputOptions:
+ outputContributingVariantsOnly: true
+ numGenes: 50
+ outputFormats:
+ - "HTML"
+ - "VCF"
+ - "TSV_GENE"
+ - "TSV_VARIANT"
+ - "JSON"
+ outputFileName: "V350145665_L04_B5EHOMdmhwXAAAA-515-exomiser-solo"
+ outputDirectory: "/home/ivanwilliamharsono/Downloads/trio_patient/exomiser"
+
+
+
+
+
+ Filtering Summary
+
+
+
+
+
+ | Filter | +Report | +Passed filter | +Failed filter | +
|---|---|---|---|
| Failed previous VCF filters | ++ + | +648 | +0 | +
| Variant effect | +
+
|
+ 648 | +0 | +
| Frequency | +
+
|
+ 648 | +0 | +
| Pathogenicity | +
+
|
+ 648 | +0 | +
| Inheritance | +
+
|
+ 500 | +0 | +
+
+
+
+
+
+
+ Variant Type Distribution
+
+
+
+
+
+ | Variant Type | + +Proband | + +
|---|---|
| FRAMESHIFT_ELONGATION | + +4 | + +
| FRAMESHIFT_TRUNCATION | + +3 | + +
| FRAMESHIFT_VARIANT | + +2 | + +
| INTERNAL_FEATURE_ELONGATION | + +0 | + +
| FEATURE_TRUNCATION | + +0 | + +
| MNV | + +0 | + +
| STOP_GAINED | + +6 | + +
| STOP_LOST | + +0 | + +
| START_LOST | + +0 | + +
| SPLICE_ACCEPTOR_VARIANT | + +1 | + +
| SPLICE_DONOR_VARIANT | + +1 | + +
| MISSENSE_VARIANT | + +352 | + +
| INFRAME_INSERTION | + +2 | + +
| DISRUPTIVE_INFRAME_INSERTION | + +9 | + +
| INFRAME_DELETION | + +1 | + +
| DISRUPTIVE_INFRAME_DELETION | + +12 | + +
| FIVE_PRIME_UTR_TRUNCATION | + +0 | + +
| THREE_PRIME_UTR_TRUNCATION | + +0 | + +
| SPLICE_REGION_VARIANT | + +49 | + +
| STOP_RETAINED_VARIANT | + +0 | + +
| INITIATOR_CODON_VARIANT | + +0 | + +
| SYNONYMOUS_VARIANT | + +206 | + +
| CODING_TRANSCRIPT_INTRON_VARIANT | + +0 | + +
| FIVE_PRIME_UTR_EXON_VARIANT | + +0 | + +
| THREE_PRIME_UTR_EXON_VARIANT | + +0 | + +
| FIVE_PRIME_UTR_INTRON_VARIANT | + +0 | + +
| THREE_PRIME_UTR_INTRON_VARIANT | + +0 | + +
| NON_CODING_TRANSCRIPT_EXON_VARIANT | + +0 | + +
| NON_CODING_TRANSCRIPT_INTRON_VARIANT | + +0 | + +
| UPSTREAM_GENE_VARIANT | + +0 | + +
| DOWNSTREAM_GENE_VARIANT | + +0 | + +
| INTERGENIC_VARIANT | + +0 | + +
| REGULATORY_REGION_VARIANT | + +0 | + +
+
+
+
+ Prioritised Genes
+
+
+
+
+
+
+
+
+ + + GBE1 + +
+
+
+ Exomiser Score: 0.931 + (p=8.4E-4) +
+
+
+ Phenotype Score: 0.658
+
+
+ Variant Score: 0.985
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.639 to Glycogen storage disease IV associated with GBE1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001433, Hepatosplenomegaly
- HP:0001903, Anemia - HP:0001433, Hepatosplenomegaly
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production - HP:0001433, Hepatosplenomegaly
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001433, Hepatosplenomegaly
- HP:0001396, Cholestasis - HP:0001399, Hepatic failure
- HP:0001410, Decreased liver function - HP:0001399, Hepatic failure
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001399, Hepatic failure
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001638, Cardiomyopathy
- HP:0200114, Metabolic alkalosis - HP:0000969, Edema
- HP:0003073, Hypoalbuminemia - HP:0040081, Abnormal circulating creatine kinase concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0040081, Abnormal circulating creatine kinase concentration
- HP:0001873, Thrombocytopenia - HP:0001433, Hepatosplenomegaly
- HP:0002151, Increased serum lactate - HP:0040081, Abnormal circulating creatine kinase concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001394, Cirrhosis
- HP:0004333, Bone-marrow foam cells - HP:0001433, Hepatosplenomegaly
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Phenotypic similarity 0.658 to mouse mutant involving GBE1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0003333, liver fibrosis
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0003333, liver fibrosis
- HP:0001410, Decreased liver function - MP:0003333, liver fibrosis
- HP:0002910, Elevated hepatic transaminase - MP:0003333, liver fibrosis
- HP:0001399, Hepatic failure - MP:0003333, liver fibrosis
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0010090, increased circulating creatine kinase level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0010090, increased circulating creatine kinase level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0003333, liver fibrosis
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0003333, liver fibrosis
- HP:0002366, Abnormal lower motor neuron morphology - MP:0014074, increased brain glycogen level
- HP:0006568, Increased hepatic glycogen content - MP:0010400, increased liver glycogen level
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.508 in interactome to PPP1R3C and phenotypic similarity 0.604 to mouse mutant of PPP1R3C.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0010398, decreased liver glycogen level
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0010398, decreased liver glycogen level
- HP:0001410, Decreased liver function - MP:0010398, decreased liver glycogen level
- HP:0002910, Elevated hepatic transaminase - MP:0010398, decreased liver glycogen level
- HP:0001399, Hepatic failure - MP:0010398, decreased liver glycogen level
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0002833, increased heart weight
- HP:0200114, Metabolic alkalosis - MP:0005669, increased circulating leptin level
- HP:0003073, Hypoalbuminemia - MP:0005669, increased circulating leptin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0001552, increased circulating triglyceride level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005669, increased circulating leptin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0010398, decreased liver glycogen level
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0010398, decreased liver glycogen level
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0010398, decreased liver glycogen level
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 1.57 (p-value: 0.000060)
-
+
- Known diseases: +
- OMIM:232500 Glycogen storage disease IV - autosomal recessive +
- OMIM:263570 Polyglucosan body disease, adult form - autosomal recessive +
- ORPHA:206583 Adult polyglucosan body disease - autosomal recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.931 + (p=8.4E-4) +
+
+
+ Phenotype Score: 0.658 +
+
+
+ Variant Score: 0.985 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.639 to OMIM:232500 Glycogen storage disease IV + +
- Phenotypic similarity 0.475 to OMIM:263570 Polyglucosan body disease, adult form + +
- Phenotypic similarity 0.203 to ORPHA:206583 Adult polyglucosan body disease + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 3-81648954-C-G [1/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, PP3_Moderate, PP4]
+
+
+
+
+ Variant score: 0.985
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + GBE1:ENST00000429644.7:c.593G>C:p.(Arg198Thr) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9849782 + +
- REVEL: 0.873 +
- MVP: 0.985 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + ABCG5 + +
+
+
+ Exomiser Score: 0.914 + (p=1.4E-3) +
+
+
+ Phenotype Score: 0.623
+
+
+ Variant Score: 1.000
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.537 to Homozygous familial hypercholesterolemia associated with ABCG5.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001397, Hepatic steatosis
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0001397, Hepatic steatosis
- HP:0001410, Decreased liver function - HP:0001397, Hepatic steatosis
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001397, Hepatic steatosis
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0004381, Supravalvular aortic stenosis
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - HP:0003077, Hyperlipidemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003141, Increased LDL cholesterol concentration
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0003077, Hyperlipidemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0001138, Optic neuropathy
- HP:0006568, Increased hepatic glycogen content - HP:0001397, Hepatic steatosis
- HP:0004333, Bone-marrow foam cells - HP:0004416, Precocious atherosclerosis
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.623 to mouse mutant involving ABCG5.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000229, abnormal megakaryocyte differentiation
- HP:0001903, Anemia - MP:0001585, hemolytic anemia
- HP:0001541, Ascites - MP:0005606, increased bleeding time
- HP:0010972, Anemia of inadequate production - MP:0000229, abnormal megakaryocyte differentiation
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0002417, abnormal megakaryocyte morphology
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - MP:0002417, abnormal megakaryocyte morphology
- HP:0001642, Pulmonic stenosis - MP:0003141, cardiac fibrosis
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000180, abnormal circulating cholesterol level
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0005065, abnormal neutrophil morphology
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.525 in interactome to ABCC6 and phenotypic similarity 0.632 to Generalized arterial calcification of infancy associated with ABCC6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0006559, Hepatic calcification
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0004912, Hypophosphatemic rickets
- HP:0001396, Cholestasis - HP:0006559, Hepatic calcification
- HP:0001410, Decreased liver function - HP:0006559, Hepatic calcification
- HP:0002910, Elevated hepatic transaminase - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0001399, Hepatic failure - HP:0006559, Hepatic calcification
- HP:0000938, Osteopenia - HP:0002749, Osteomalacia
- HP:0001642, Pulmonic stenosis - HP:0001714, Ventricular hypertrophy
- HP:0200114, Metabolic alkalosis - HP:0000969, Edema
- HP:0003073, Hypoalbuminemia - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0003233, Decreased HDL cholesterol concentration - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0000969, Edema
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0006559, Hepatic calcification
- HP:0004333, Bone-marrow foam cells - HP:0002647, Aortic dissection
- HP:0001531, Failure to thrive in infancy - HP:0001531, Failure to thrive in infancy
- Proximity score 0.525 in interactome to ABCC6 and phenotypic similarity 0.489 to mouse mutant of ABCC6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005553, increased circulating creatinine level
- HP:0003073, Hypoalbuminemia - MP:0000186, decreased circulating HDL cholesterol level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000186, decreased circulating HDL cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005553, increased circulating creatinine level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0006133, calcified artery
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.525 in interactome to ABCC6 and phenotypic similarity 0.302 to fish mutant of ABCC6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0000038, pericardium edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - ZP:0013900, bone mineralization increased occurrence, abnormal
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - ZP:0013900, bone mineralization increased occurrence, abnormal
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 1.59 (p-value: 0.002410)
-
+
- Known diseases: +
- OMIM:618666 Sitosterolemia 2 - autosomal recessive +
- ORPHA:391665 Homozygous familial hypercholesterolemia - autosomal dominant/recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.914 + (p=1.4E-3) +
+
+
+ Phenotype Score: 0.623 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.537 to ORPHA:391665 Homozygous familial hypercholesterolemia + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ FRAMESHIFT_ELONGATION
+ INS
+ 2-43828041-G-GC [0/1]
+
+
+ rs762031825
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ABCG5:ENST00000405322.8:c.575dup:p.(Ile193Hisfs*5) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- ExAC NFE: 0.0030% +
+
+
+
+
+
+
+
+ + + FBN2 + +
+
+
+ Exomiser Score: 0.882 + (p=2.7E-3) +
+
+
+ Phenotype Score: 0.634
+
+
+ Variant Score: 0.948
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.474 to Contractural arachnodactyly, congenital associated with FBN2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0000938, Osteopenia
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - HP:0000938, Osteopenia
- HP:0001642, Pulmonic stenosis - HP:0001647, Bicuspid aortic valve
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - HP:0002616, Aortic root aneurysm
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.634 to mouse mutant involving FBN2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000598, abnormal liver morphology
- HP:0001903, Anemia - MP:0003179, thrombocytopenia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0003179, thrombocytopenia
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0003795, abnormal bone structure
- HP:0001396, Cholestasis - MP:0000598, abnormal liver morphology
- HP:0001410, Decreased liver function - MP:0000598, abnormal liver morphology
- HP:0002910, Elevated hepatic transaminase - MP:0000598, abnormal liver morphology
- HP:0001399, Hepatic failure - MP:0000598, abnormal liver morphology
- HP:0000938, Osteopenia - MP:0003795, abnormal bone structure
- HP:0001642, Pulmonic stenosis - MP:0000266, abnormal heart morphology
- HP:0200114, Metabolic alkalosis - MP:0002968, increased circulating alkaline phosphatase level
- HP:0003073, Hypoalbuminemia - MP:0008805, decreased circulating amylase level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0008805, decreased circulating amylase level
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate - MP:0002968, increased circulating alkaline phosphatase level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000598, abnormal liver morphology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000598, abnormal liver morphology
- HP:0002366, Abnormal lower motor neuron morphology - MP:0002152, abnormal brain morphology
- HP:0006568, Increased hepatic glycogen content - MP:0000598, abnormal liver morphology
- HP:0004333, Bone-marrow foam cells - MP:0003179, thrombocytopenia
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.227 to zebrafish mutant involving FBN2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0001452, trunk edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - ZP:0005691, dorsal aorta decreased diameter, abnormal
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to ADAM19 and phenotypic similarity 0.665 to mouse mutant of ADAM19.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002754, dilated heart right ventricle
- HP:0001903, Anemia -
- HP:0001541, Ascites - MP:0001785, edema
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0006128, pulmonary valve stenosis
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0000273, overriding aortic valve
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to ADAM19 and phenotypic similarity 0.249 to fish mutant of ADAM19.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0107084, hindbrain decreased magnitude axonogenesis, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.61 (p-value: 0.988800)
-
+
- Known diseases: +
- OMIM:121050 Contractural arachnodactyly, congenital - autosomal dominant +
- OMIM:616118 Macular degeneration, early-onset - autosomal dominant +
- ORPHA:115 Congenital contractural arachnodactyly - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.882 + (p=2.7E-3) +
+
+
+ Phenotype Score: 0.634 +
+
+
+ Variant Score: 0.948 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.474 to OMIM:121050 Contractural arachnodactyly, congenital + +
- Phenotypic similarity 0.293 to ORPHA:115 Congenital contractural arachnodactyly + +
- Phenotypic similarity 0.121 to OMIM:616118 Macular degeneration, early-onset + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 5-128301399-T-C [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, PP3_Moderate]
+
+
+
+
+ Variant score: 0.948
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + FBN2:ENST00000262464.9:c.6029A>G:p.(Asp2010Gly) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.94782615 + +
- REVEL: 0.881 +
- MVP: 0.948 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + GRN + +
+
+
+ Exomiser Score: 0.838 + (p=5.0E-3) +
+
+
+ Phenotype Score: 0.555
+
+
+ Variant Score: 0.998
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.538 to Progressive non-fluent aphasia associated with GRN.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0002366, Abnormal lower motor neuron morphology
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - HP:0001297, Stroke
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.555 to mouse mutant involving GRN.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0008986, abnormal liver parenchyma morphology
- HP:0001903, Anemia - MP:0008918, microgliosis
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0008918, microgliosis
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0008918, microgliosis
- HP:0001396, Cholestasis - MP:0010080, abnormal hepatocyte physiology
- HP:0001410, Decreased liver function - MP:0010080, abnormal hepatocyte physiology
- HP:0002910, Elevated hepatic transaminase - MP:0010080, abnormal hepatocyte physiology
- HP:0001399, Hepatic failure - MP:0010080, abnormal hepatocyte physiology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0008918, microgliosis
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0010080, abnormal hepatocyte physiology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0010080, abnormal hepatocyte physiology
- HP:0002366, Abnormal lower motor neuron morphology - MP:0002152, abnormal brain morphology
- HP:0006568, Increased hepatic glycogen content - MP:0008986, abnormal liver parenchyma morphology
- HP:0004333, Bone-marrow foam cells - MP:0008918, microgliosis
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.346 to zebrafish mutant involving GRN.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - ZP:0000720, liver decreased size, abnormal
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - ZP:0004503, liver morphogenesis disrupted, abnormal
- HP:0001410, Decreased liver function - ZP:0004503, liver morphogenesis disrupted, abnormal
- HP:0002910, Elevated hepatic transaminase - ZP:0004503, liver morphogenesis disrupted, abnormal
- HP:0001399, Hepatic failure - ZP:0004503, liver morphogenesis disrupted, abnormal
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - ZP:0004503, liver morphogenesis disrupted, abnormal
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - ZP:0004503, liver morphogenesis disrupted, abnormal
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0002078, spinal cord decreased length, abnormal
- HP:0006568, Increased hepatic glycogen content - ZP:0004501, hepatocyte differentiation disrupted, abnormal
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.26 (p-value: 0.763320)
-
+
- Known diseases: +
- OMIM:607485 Aphasia, primary progressive - autosomal dominant +
- OMIM:614706 Ceroid lipofuscinosis, neuronal, 11 - autosomal recessive +
- ORPHA:100069 Semantic dementia (susceptibility) +
- ORPHA:100070 Progressive non-fluent aphasia (susceptibility) +
- ORPHA:275864 Behavioral variant of frontotemporal dementia (susceptibility) +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.838 + (p=5.0E-3) +
+
+
+ Phenotype Score: 0.555 +
+
+
+ Variant Score: 0.998 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.538 to ORPHA:100070 Progressive non-fluent aphasia + +
- Phenotypic similarity 0.252 to OMIM:607485 Aphasia, primary progressive + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 17-44350469-T-C [0/1]
+
+
+ rs774067739
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Strong]
+
+
+
+
+ Variant score: 0.998
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + GRN:ENST00000053867.8:c.490T>C:p.(Cys164Arg) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9999497 + +
- REVEL: 0.940 +
- MVP: 1.000 +
+
+
+ -
+
- Frequency Data: + +
- ExAC EAS: 0.0116% +
+
+
+
+
+
+
+
+ + + FABP2 + +
+
+
+ Exomiser Score: 0.785 + (p=8.3E-3) +
+
+
+ Phenotype Score: 0.520
+
+
+ Variant Score: 1.000
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.520 to mouse mutant involving FABP2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002981, increased liver weight
- HP:0001903, Anemia -
- HP:0001541, Ascites - MP:0002981, increased liver weight
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0003402, decreased liver weight
- HP:0001410, Decreased liver function - MP:0003402, decreased liver weight
- HP:0002910, Elevated hepatic transaminase - MP:0003402, decreased liver weight
- HP:0001399, Hepatic failure - MP:0003402, decreased liver weight
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005669, increased circulating leptin level
- HP:0003073, Hypoalbuminemia - MP:0005669, increased circulating leptin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005179, decreased circulating cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005669, increased circulating leptin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0003402, decreased liver weight
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0003402, decreased liver weight
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0003402, decreased liver weight
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0005658, increased susceptibility to diet-induced obesity
- Proximity score 0.500 in interactome to SLCO1B3 and phenotypic similarity 0.524 to Rotor syndrome associated with SLCO1B3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0031137, Storage in hepatocytes
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0000952, Jaundice
- HP:0001410, Decreased liver function - HP:0000952, Jaundice
- HP:0002910, Elevated hepatic transaminase - HP:0012379, Abnormal circulating enzyme concentration or activity
- HP:0001399, Hepatic failure - HP:0000952, Jaundice
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0002904, Hyperbilirubinemia
- HP:0003073, Hypoalbuminemia - HP:0002904, Hyperbilirubinemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0002904, Hyperbilirubinemia
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0002904, Hyperbilirubinemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0012379, Abnormal circulating enzyme concentration or activity
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0012379, Abnormal circulating enzyme concentration or activity
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0031137, Storage in hepatocytes
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to SLCO1B3 and phenotypic similarity 0.617 to mouse mutant of SLCO1B3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000609, abnormal liver physiology
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0000609, abnormal liver physiology
- HP:0001410, Decreased liver function - MP:0000609, abnormal liver physiology
- HP:0002910, Elevated hepatic transaminase - MP:0000609, abnormal liver physiology
- HP:0001399, Hepatic failure - MP:0000609, abnormal liver physiology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005568, increased circulating total protein level
- HP:0003073, Hypoalbuminemia - MP:0000199, abnormal circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005178, increased circulating cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005344, increased circulating bilirubin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000609, abnormal liver physiology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000609, abnormal liver physiology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000609, abnormal liver physiology
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.785 + (p=8.3E-3) +
+
+
+ Phenotype Score: 0.520 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ FRAMESHIFT_TRUNCATION
+ DEL
+ 4-119320758-TTGAC-T [0/1]
+
+
+ rs780659556
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + FABP2:ENST00000274024.4:c.148_151del:p.(Val50Lysfs*23) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0008% +
- ExAC NFE: 0.0030% +
- gnomAD_E_NFE: 0.0027% +
+
+
+
+
+
+
+
+ + + ATXN3 + +
+
+
+ Exomiser Score: 0.763 + (p=1.0E-2) +
+
+
+ Phenotype Score: 0.507
+
+
+ Variant Score: 1.000
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.271 to Machado-Joseph disease associated with ATXN3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0002171, Gliosis
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0002503, Spinocerebellar tract degeneration
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.284 to mouse mutant involving ATXN3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005343, increased circulating aspartate transaminase level
- HP:0003073, Hypoalbuminemia - MP:0005343, increased circulating aspartate transaminase level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005343, increased circulating aspartate transaminase level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005343, increased circulating aspartate transaminase level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.507 in interactome to TWNK and phenotypic similarity 0.609 to Autosomal dominant progressive external ophthalmoplegia associated with TWNK.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001392, Abnormality of the liver
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0000969, Edema
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0000939, Osteoporosis
- HP:0001396, Cholestasis - HP:0001392, Abnormality of the liver
- HP:0001410, Decreased liver function - HP:0001392, Abnormality of the liver
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001392, Abnormality of the liver
- HP:0000938, Osteopenia - HP:0000939, Osteoporosis
- HP:0001642, Pulmonic stenosis - HP:0001712, Left ventricular hypertrophy
- HP:0200114, Metabolic alkalosis - HP:0002151, Increased serum lactate
- HP:0003073, Hypoalbuminemia - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0002151, Increased serum lactate
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology - HP:0009830, Peripheral neuropathy
- HP:0006568, Increased hepatic glycogen content - HP:0000819, Diabetes mellitus
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- PhenIX semantic similarity score: 0.38 (p-value: 0.943010)
-
+
- Known diseases: +
- OMIM:109150 Machado-Joseph disease - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.763 + (p=1.0E-2) +
+
+
+ Phenotype Score: 0.507 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.271 to OMIM:109150 Machado-Joseph disease + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ FRAMESHIFT_ELONGATION
+ INS
+ 14-92071010-C-CTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG [0/1]
+
+
+ rs1555397062
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+ LIKELY_PATHOGENIC
+
+
+
+ [PVS1, PM2_Supporting]
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ATXN3:ENST00000644486.2:c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA:p.(Gly306Glnfs*38) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + CILK1 + +
+
+
+ Exomiser Score: 0.749 + (p=1.2E-2) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 1.000
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.220 to Endocrine-cerebroosteodysplasia associated with CILK1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0000835, Adrenal hypoplasia
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0032471, Focal polymicrogyria
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0000835, Adrenal hypoplasia
- HP:0001410, Decreased liver function - HP:0000835, Adrenal hypoplasia
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0000835, Adrenal hypoplasia
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0032471, Focal polymicrogyria
- HP:0006568, Increased hepatic glycogen content - HP:0000835, Adrenal hypoplasia
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.370 to mouse mutant involving CILK1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - MP:0001785, edema
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0002896, abnormal bone mineralization
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - MP:0002896, abnormal bone mineralization
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - MP:0012676, dilated brain ventricle
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0000547, short limbs
- Proximity score 0.500 in interactome to CPOX and phenotypic similarity 0.498 to Harderoporphyria associated with CPOX.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001878, Hemolytic anemia
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001878, Hemolytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001878, Hemolytic anemia
- HP:0001396, Cholestasis - HP:0006579, Prolonged neonatal jaundice
- HP:0001410, Decreased liver function - HP:0002240, Hepatomegaly
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0002240, Hepatomegaly
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0003265, Neonatal hyperbilirubinemia
- HP:0003073, Hypoalbuminemia - HP:0003281, Increased circulating ferritin concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003281, Increased circulating ferritin concentration
- HP:0001873, Thrombocytopenia - HP:0001923, Reticulocytosis
- HP:0002151, Increased serum lactate - HP:0003265, Neonatal hyperbilirubinemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells - HP:0001878, Hemolytic anemia
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to CPOX and phenotypic similarity 0.675 to mouse mutant of CPOX.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000691, enlarged spleen
- HP:0001903, Anemia - MP:0002591, decreased mean corpuscular volume
- HP:0001541, Ascites - MP:0000691, enlarged spleen
- HP:0010972, Anemia of inadequate production - MP:0002810, microcytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0011178, increased erythroblast number
- HP:0001396, Cholestasis - MP:0008476, increased spleen red pulp amount
- HP:0001410, Decreased liver function - MP:0008476, increased spleen red pulp amount
- HP:0002910, Elevated hepatic transaminase - MP:0008476, increased spleen red pulp amount
- HP:0001399, Hepatic failure - MP:0008476, increased spleen red pulp amount
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0011890, increased circulating ferritin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0011890, increased circulating ferritin level
- HP:0001873, Thrombocytopenia - MP:0002447, abnormal erythrocyte morphology
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0008476, increased spleen red pulp amount
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0008476, increased spleen red pulp amount
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0008476, increased spleen red pulp amount
- HP:0004333, Bone-marrow foam cells - MP:0002447, abnormal erythrocyte morphology
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.08 (p-value: 1.000000)
-
+
- Known diseases: +
- OMIM:612651 Endocrine-cerebroosteodysplasia - autosomal recessive +
- OMIM:617924 Epilepsy, juvenile myoclonic, susceptibility to, 10 (susceptibility) +
- ORPHA:307 Juvenile myoclonic epilepsy - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.749 + (p=1.2E-2) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ FRAMESHIFT_TRUNCATION
+ DEL
+ 6-53006378-TC-T [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + CILK1:ENST00000676107.1:c.1680del:p.(Glu563Lysfs*11) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.564 + (p=7.8E-2) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.909 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.220 to OMIM:612651 Endocrine-cerebroosteodysplasia + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ FRAMESHIFT_TRUNCATION
+ DEL
+ 6-53006378-TC-T [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+ LIKELY_PATHOGENIC
+
+
+
+ [PVS1, PM2_Supporting]
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + CILK1:ENST00000676107.1:c.1680del:p.(Glu563Lysfs*11) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+ MISSENSE_VARIANT
+ SNV
+ 6-53006371-T-C [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.818
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + CILK1:ENST00000676107.1:c.1688A>G:p.(Glu563Gly) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8177741 + +
- REVEL: 0.584 +
- MVP: 0.818 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + DIAPH2 + +
+
+
+ Exomiser Score: 0.749 + (p=1.2E-2) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 1.000
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.177 to ?Premature ovarian failure 2A associated with DIAPH2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0008232, Elevated circulating follicle stimulating hormone level
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0008232, Elevated circulating follicle stimulating hormone level
- HP:0001410, Decreased liver function - HP:0008209, Premature ovarian insufficiency
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0008209, Premature ovarian insufficiency
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - HP:0008232, Elevated circulating follicle stimulating hormone level
- HP:0003233, Decreased HDL cholesterol concentration - HP:0008232, Elevated circulating follicle stimulating hormone level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0008232, Elevated circulating follicle stimulating hormone level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0008232, Elevated circulating follicle stimulating hormone level
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.222 to mouse mutant involving DIAPH2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0001566, increased circulating phosphate level
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0001566, increased circulating phosphate level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to SLC20A1 and phenotypic similarity 0.604 to mouse mutant of SLC20A1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000691, enlarged spleen
- HP:0001903, Anemia - MP:0001577, anemia
- HP:0001541, Ascites - MP:0000691, enlarged spleen
- HP:0010972, Anemia of inadequate production - MP:0000245, abnormal erythropoiesis
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0002896, abnormal bone mineralization
- HP:0001396, Cholestasis - MP:0000689, abnormal spleen morphology
- HP:0001410, Decreased liver function - MP:0000689, abnormal spleen morphology
- HP:0002910, Elevated hepatic transaminase - MP:0000689, abnormal spleen morphology
- HP:0001399, Hepatic failure - MP:0000689, abnormal spleen morphology
- HP:0000938, Osteopenia - MP:0002896, abnormal bone mineralization
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0002874, decreased hemoglobin content
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005280, abnormal fatty acids level
- HP:0001873, Thrombocytopenia - MP:0002875, decreased erythrocyte cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000689, abnormal spleen morphology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000689, abnormal spleen morphology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000689, abnormal spleen morphology
- HP:0004333, Bone-marrow foam cells - MP:0000245, abnormal erythropoiesis
- HP:0001531, Failure to thrive in infancy - MP:0001732, postnatal growth retardation
- PhenIX semantic similarity score: 0.01 (p-value: 0.858070)
-
+
- Known diseases: +
- OMIM:300511 ?Premature ovarian failure 2A (unconfirmed) +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+ X_DOMINANT
+
+
+ Exomiser Score: + 0.749 + (p=1.2E-2) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.177 to OMIM:300511 ?Premature ovarian failure 2A + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ STOP_GAINED
+ SNV
+ X-97348134-C-T [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+ LIKELY_PATHOGENIC
+
+
+
+ [PVS1, PM2_Supporting]
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + DIAPH2:ENST00000324765.13:c.2863C>T:p.(Arg955*) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ X_RECESSIVE
+
+
+ Exomiser Score: + 0.182 + (p=2.3E-1) +
+
+
+ Phenotype Score: 0.250 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ STOP_GAINED
+ SNV
+ X-97348134-C-T [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + DIAPH2:ENST00000324765.13:c.2863C>T:p.(Arg955*) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + ANKFN1 + +
+
+
+ Exomiser Score: 0.749 + (p=1.3E-2) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 1.000
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.265 to mouse mutant involving ANKFN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.500 in interactome to SIRPG and phenotypic similarity 0.619 to mouse mutant of SIRPG.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002628, hepatic steatosis
- HP:0001903, Anemia - MP:0003179, thrombocytopenia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0003179, thrombocytopenia
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0008254, increased megakaryocyte cell number
- HP:0001396, Cholestasis - MP:0002628, hepatic steatosis
- HP:0001410, Decreased liver function - MP:0002628, hepatic steatosis
- HP:0002910, Elevated hepatic transaminase - MP:0002628, hepatic steatosis
- HP:0001399, Hepatic failure - MP:0002628, hepatic steatosis
- HP:0000938, Osteopenia - MP:0008254, increased megakaryocyte cell number
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002628, hepatic steatosis
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0002628, hepatic steatosis
- HP:0004333, Bone-marrow foam cells - MP:0005018, decreased T cell number
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.749 + (p=1.3E-2) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ FRAMESHIFT_VARIANT
+ DEL
+ 17-56374681-AG-A [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ANKFN1:ENST00000682825.1:c.878del:p.(Ser293Thrfs*6) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + GLT8D1 + +
+
+
+ Exomiser Score: 0.748 + (p=1.3E-2) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 1.000
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.464 to Amyotrophic lateral sclerosis associated with GLT8D1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0000217, Xerostomia
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function - HP:0000217, Xerostomia
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0000217, Xerostomia
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0000217, Xerostomia
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0000217, Xerostomia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0007373, Motor neuron atrophy
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to SRP54 and phenotypic similarity 0.676 to Shwachman-Diamond syndrome associated with SRP54.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0002240, Hepatomegaly
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001897, Normocytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0005528, Bone marrow hypocellularity
- HP:0001396, Cholestasis - HP:0002240, Hepatomegaly
- HP:0001410, Decreased liver function - HP:0001738, Exocrine pancreatic insufficiency
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001738, Exocrine pancreatic insufficiency
- HP:0000938, Osteopenia - HP:0000938, Osteopenia
- HP:0001642, Pulmonic stenosis - HP:0001627, Abnormal heart morphology
- HP:0200114, Metabolic alkalosis - HP:0012202, Increased serum bile acid concentration
- HP:0003073, Hypoalbuminemia - HP:0410289, Hypoamylasemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0012202, Increased serum bile acid concentration
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0012202, Increased serum bile acid concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells - HP:0040238, Impaired neutrophil chemotaxis
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.500 in interactome to SRP54 and phenotypic similarity 0.196 to fish mutant of SRP54.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - ZP:0002029, pancreas development disrupted, abnormal
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - ZP:0002029, pancreas development disrupted, abnormal
- HP:0001410, Decreased liver function - ZP:0002029, pancreas development disrupted, abnormal
- HP:0002910, Elevated hepatic transaminase - ZP:0002029, pancreas development disrupted, abnormal
- HP:0001399, Hepatic failure - ZP:0002029, pancreas development disrupted, abnormal
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - ZP:0002029, pancreas development disrupted, abnormal
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - ZP:0002029, pancreas development disrupted, abnormal
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - ZP:0002029, pancreas development disrupted, abnormal
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
-
+
- Known diseases: +
- ORPHA:803 Amyotrophic lateral sclerosis (susceptibility) +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.748 + (p=1.3E-2) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 1.000 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.464 to ORPHA:803 Amyotrophic lateral sclerosis + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ FRAMESHIFT_ELONGATION
+ INS
+ 3-52697811-G-GC [0/1]
+
+
+ rs754869681
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+ LIKELY_PATHOGENIC
+
+
+
+ [PVS1]
+
+
+
+
+ Variant score: 1.000
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + GLT8D1:ENST00000266014.11:c.238dup:p.(Ala80Glyfs*37) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_SAS: 0.0032% +
+
+
+
+
+
+
+
+ + + PTPN7 + +
+
+
+ Exomiser Score: 0.748 + (p=1.3E-2) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.999
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Proximity score 0.500 in interactome to DUSP16 and phenotypic similarity 0.644 to mouse mutant of DUSP16.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000691, enlarged spleen
- HP:0001903, Anemia - MP:0002875, decreased erythrocyte cell number
- HP:0001541, Ascites - MP:0000691, enlarged spleen
- HP:0010972, Anemia of inadequate production - MP:0002874, decreased hemoglobin content
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0003795, abnormal bone structure
- HP:0001396, Cholestasis - MP:0000691, enlarged spleen
- HP:0001410, Decreased liver function - MP:0000691, enlarged spleen
- HP:0002910, Elevated hepatic transaminase - MP:0000691, enlarged spleen
- HP:0001399, Hepatic failure - MP:0000691, enlarged spleen
- HP:0000938, Osteopenia - MP:0003795, abnormal bone structure
- HP:0001642, Pulmonic stenosis - MP:0002833, increased heart weight
- HP:0200114, Metabolic alkalosis - MP:0005344, increased circulating bilirubin level
- HP:0003073, Hypoalbuminemia - MP:0002874, decreased hemoglobin content
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000186, decreased circulating HDL cholesterol level
- HP:0001873, Thrombocytopenia - MP:0002875, decreased erythrocyte cell number
- HP:0002151, Increased serum lactate - MP:0005344, increased circulating bilirubin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000691, enlarged spleen
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000691, enlarged spleen
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000691, enlarged spleen
- HP:0004333, Bone-marrow foam cells - MP:0002875, decreased erythrocyte cell number
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.748 + (p=1.3E-2) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.999 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ STOP_GAINED
+ SNV
+ 1-202159294-G-A [0/1]
+
+
+ rs149516769
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.999
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + PTPN7:ENST00000691036.1:c.109C>T:p.(Arg37*) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0011% +
- ExAC NFE: 0.0030% +
- gnomAD_E_NFE: 0.0036% +
- gnomAD_G_NFE: 0.0067% +
+
+
+
+
+
+
+
+ + + ALDH1L2 + +
+
+
+ Exomiser Score: 0.666 + (p=4.3E-2) +
+
+
+ Phenotype Score: 0.503
+
+
+ Variant Score: 0.953
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.442 to mouse mutant involving ALDH1L2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002628, hepatic steatosis
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0002628, hepatic steatosis
- HP:0001410, Decreased liver function - MP:0002628, hepatic steatosis
- HP:0002910, Elevated hepatic transaminase - MP:0002628, hepatic steatosis
- HP:0001399, Hepatic failure - MP:0002628, hepatic steatosis
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration - MP:0014174, decreased fatty acid beta-oxidation
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0002628, hepatic steatosis
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.503 in interactome to DHFR and phenotypic similarity 0.632 to Megaloblastic anemia due to dihydrofolate reductase deficiency associated with DHFR.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0002240, Hepatomegaly
- HP:0001903, Anemia - HP:0005518, Increased mean corpuscular volume
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001889, Megaloblastic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001876, Pancytopenia
- HP:0001396, Cholestasis - HP:0000952, Jaundice
- HP:0001410, Decreased liver function - HP:0000952, Jaundice
- HP:0002910, Elevated hepatic transaminase - HP:0025435, Increased circulating lactate dehydrogenase concentration
- HP:0001399, Hepatic failure - HP:0000952, Jaundice
- HP:0000938, Osteopenia - HP:0001876, Pancytopenia
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0040087, Abnormal blood folate concentration
- HP:0003073, Hypoalbuminemia - HP:0040087, Abnormal blood folate concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0040087, Abnormal blood folate concentration
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0040087, Abnormal blood folate concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0025435, Increased circulating lactate dehydrogenase concentration
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0025435, Increased circulating lactate dehydrogenase concentration
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells - HP:0001876, Pancytopenia
- HP:0001531, Failure to thrive in infancy - HP:0005484, Secondary microcephaly
- Proximity score 0.503 in interactome to DHFR and phenotypic similarity 0.536 to mouse mutant of DHFR.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000600, liver hypoplasia
- HP:0001903, Anemia - MP:0002875, decreased erythrocyte cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0008813, decreased common myeloid progenitor cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0013697, decreased granulocyte monocyte progenitor cell number
- HP:0001396, Cholestasis - MP:0000603, pale liver
- HP:0001410, Decreased liver function - MP:0000603, pale liver
- HP:0002910, Elevated hepatic transaminase - MP:0000603, pale liver
- HP:0001399, Hepatic failure - MP:0000603, pale liver
- HP:0000938, Osteopenia - MP:0013697, decreased granulocyte monocyte progenitor cell number
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0002875, decreased erythrocyte cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000603, pale liver
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000603, pale liver
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000600, liver hypoplasia
- HP:0004333, Bone-marrow foam cells - MP:0009395, increased nucleated erythrocyte cell number
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.503 in interactome to DHFR and phenotypic similarity 0.318 to fish mutant of DHFR.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0001466, ventral region whole organism edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - ZP:0000486, cardiac ventricle structure, abnormal
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - ZP:0017548, axis elongation decreased rate, abnormal
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.666 + (p=4.3E-2) +
+
+
+ Phenotype Score: 0.503 +
+
+
+ Variant Score: 0.953 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 12-105038171-G-A [0/1]
+
+
+ rs373348266
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.953
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ALDH1L2:ENST00000258494.14:c.2077C>T:p.(Leu693Phe) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9617639 + +
- REVEL: 0.826 +
- MVP: 0.962 +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0121% +
- ESP AA: 0.0681% +
- ESP All: 0.0231% +
- ExAC AFR: 0.0484% +
- gnomAD_E_AFR: 0.0654% +
- gnomAD_G_AFR: 0.0230% +
+
+
+
+
+
+
+
+ + + NOX5 + +
+
+
+ Exomiser Score: 0.663 + (p=4.4E-2) +
+
+
+ Phenotype Score: 0.501
+
+
+ Variant Score: 0.954
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.123 to zebrafish mutant involving NOX5.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0005361, cranial nerve II decreased thickness, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to NOS3 and phenotypic similarity 0.527 to Hypertension, pregnancy-induced associated with NOS3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001873, Thrombocytopenia
- HP:0001903, Anemia - HP:0001873, Thrombocytopenia
- HP:0001541, Ascites - HP:0000969, Edema
- HP:0010972, Anemia of inadequate production - HP:0001873, Thrombocytopenia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001873, Thrombocytopenia
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0000822, Hypertension
- HP:0200114, Metabolic alkalosis - HP:0000969, Edema
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0000969, Edema
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - HP:0001873, Thrombocytopenia
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to NOS3 and phenotypic similarity 0.605 to mouse mutant of NOS3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000607, abnormal hepatocyte morphology
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0001125, abnormal oocyte morphology
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0009345, abnormal trabecular bone thickness
- HP:0001396, Cholestasis - MP:0000609, abnormal liver physiology
- HP:0001410, Decreased liver function - MP:0000609, abnormal liver physiology
- HP:0002910, Elevated hepatic transaminase - MP:0000609, abnormal liver physiology
- HP:0001399, Hepatic failure - MP:0000609, abnormal liver physiology
- HP:0000938, Osteopenia - MP:0000063, decreased bone mineral density
- HP:0001642, Pulmonic stenosis - MP:0003921, abnormal heart left ventricle morphology
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0002727, decreased circulating insulin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005182, increased circulating estradiol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000609, abnormal liver physiology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000609, abnormal liver physiology
- HP:0002366, Abnormal lower motor neuron morphology - MP:0002882, abnormal neuron morphology
- HP:0006568, Increased hepatic glycogen content - MP:0002628, hepatic steatosis
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.663 + (p=4.4E-2) +
+
+
+ Phenotype Score: 0.501 +
+
+
+ Variant Score: 0.954 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 15-69035456-G-A [0/1]
+
+
+ rs748636955
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.954
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + NOX5:ENST00000388866.8:c.958G>A:p.(Val320Met) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9551393 + +
- REVEL: 0.328 +
- MVP: 0.955 +
+
+
+ -
+
- Frequency Data: + +
- ExAC AMR: 0.0087% +
- ExAC NFE: 0.0030% +
- gnomAD_E_NFE: 0.0018% +
- gnomAD_E_SAS: 0.0032% +
+
+
+
+
+
+
+
+ + + PROZ + +
+
+
+ Exomiser Score: 0.647 + (p=5.0E-2) +
+
+
+ Phenotype Score: 0.501
+
+
+ Variant Score: 0.946
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.223 to mouse mutant involving PROZ.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - MP:0031121, increased susceptibility to induced thrombosis
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to ABCC6 and phenotypic similarity 0.632 to Generalized arterial calcification of infancy associated with ABCC6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0006559, Hepatic calcification
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0004912, Hypophosphatemic rickets
- HP:0001396, Cholestasis - HP:0006559, Hepatic calcification
- HP:0001410, Decreased liver function - HP:0006559, Hepatic calcification
- HP:0002910, Elevated hepatic transaminase - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0001399, Hepatic failure - HP:0006559, Hepatic calcification
- HP:0000938, Osteopenia - HP:0002749, Osteomalacia
- HP:0001642, Pulmonic stenosis - HP:0001714, Ventricular hypertrophy
- HP:0200114, Metabolic alkalosis - HP:0000969, Edema
- HP:0003073, Hypoalbuminemia - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0003233, Decreased HDL cholesterol concentration - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0000969, Edema
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0010639, Elevated alkaline phosphatase of bone origin
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0006559, Hepatic calcification
- HP:0004333, Bone-marrow foam cells - HP:0002647, Aortic dissection
- HP:0001531, Failure to thrive in infancy - HP:0001531, Failure to thrive in infancy
- Proximity score 0.501 in interactome to ABCC6 and phenotypic similarity 0.489 to mouse mutant of ABCC6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005553, increased circulating creatinine level
- HP:0003073, Hypoalbuminemia - MP:0000186, decreased circulating HDL cholesterol level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000186, decreased circulating HDL cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005553, increased circulating creatinine level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0006133, calcified artery
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to ABCC6 and phenotypic similarity 0.302 to fish mutant of ABCC6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0000038, pericardium edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - ZP:0013900, bone mineralization increased occurrence, abnormal
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - ZP:0013900, bone mineralization increased occurrence, abnormal
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.647 + (p=5.0E-2) +
+
+
+ Phenotype Score: 0.501 +
+
+
+ Variant Score: 0.946 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 13-113164614-G-T [0/1]
+
+
+ rs375926497
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.946
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + PROZ:ENST00000375547.7:c.475G>T:p.(Gly159Cys) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.95580864 + +
- REVEL: 0.537 +
- MVP: 0.956 +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0156% +
- TOPMed: 0.0004% +
- ExAC EAS: 0.0701% +
- ExAC NFE: 0.0015% +
- gnomAD_E_EAS: 0.0464% +
- gnomAD_E_NFE: 0.0009% +
+
+
+
+
+
+
+
+ + + SCN4A + +
+
+
+ Exomiser Score: 0.644 + (p=5.1E-2) +
+
+
+ Phenotype Score: 0.502
+
+
+ Variant Score: 0.944
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.526 to Congenital myopathy 22B, severe fetal associated with SCN4A.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0002240, Hepatomegaly
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0002240, Hepatomegaly
- HP:0001410, Decreased liver function - HP:0002240, Hepatomegaly
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0002240, Hepatomegaly
- HP:0000938, Osteopenia - HP:0002987, Elbow flexion contracture
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0002202, Pleural effusion
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0002202, Pleural effusion
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - HP:0001790, Nonimmune hydrops fetalis
- Phenotypic similarity 0.415 to mouse mutant involving SCN4A.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0008935, decreased mean platelet volume
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0008935, decreased mean platelet volume
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0002910, Elevated hepatic transaminase - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0001399, Hepatic failure - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0008806, increased circulating amylase level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0008806, increased circulating amylase level
- HP:0001873, Thrombocytopenia - MP:0008935, decreased mean platelet volume
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0008935, decreased mean platelet volume
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.502 in interactome to GLRB and phenotypic similarity 0.163 to Hereditary hyperekplexia associated with GLRB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - HP:0001387, Joint stiffness
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.502 in interactome to GLRB and phenotypic similarity 0.618 to mouse mutant of GLRB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0004952, increased spleen weight
- HP:0001903, Anemia - MP:0000219, increased neutrophil cell number
- HP:0001541, Ascites - MP:0004952, increased spleen weight
- HP:0010972, Anemia of inadequate production - MP:0000219, increased neutrophil cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0000219, increased neutrophil cell number
- HP:0001396, Cholestasis - MP:0004952, increased spleen weight
- HP:0001410, Decreased liver function - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0002910, Elevated hepatic transaminase - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0001399, Hepatic failure - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0002833, increased heart weight
- HP:0200114, Metabolic alkalosis - MP:0005343, increased circulating aspartate transaminase level
- HP:0003073, Hypoalbuminemia - MP:0005419, decreased circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005419, decreased circulating serum albumin level
- HP:0001873, Thrombocytopenia - MP:0000219, increased neutrophil cell number
- HP:0002151, Increased serum lactate - MP:0005343, increased circulating aspartate transaminase level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0004952, increased spleen weight
- HP:0004333, Bone-marrow foam cells - MP:0000219, increased neutrophil cell number
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.79 (p-value: 0.991310)
-
+
- Known diseases: +
- OMIM:168300 Paramyotonia congenita - autosomal dominant +
- OMIM:170500 Hyperkalemic periodic paralysis - autosomal dominant +
- OMIM:608390 Myotonia congenita, atypical, acetazolamide-responsive - autosomal dominant +
- OMIM:613345 Hypokalemic periodic paralysis, type 2 - autosomal dominant +
- OMIM:614198 Myasthenic syndrome, congenital, 16 - autosomal recessive +
- OMIM:620351 Congenital myopathy 22A, classic - autosomal recessive +
- OMIM:620369 Congenital myopathy 22B, severe fetal - autosomal recessive +
- ORPHA:681 Hypokalemic periodic paralysis - autosomal dominant +
- ORPHA:682 Hyperkalemic periodic paralysis - autosomal dominant +
- ORPHA:684 Paramyotonia congenita of Von Eulenburg - autosomal dominant +
- ORPHA:98913 Postsynaptic congenital myasthenic syndromes - autosomal recessive +
- ORPHA:99734 Myotonia fluctuans - autosomal dominant +
- ORPHA:99735 Myotonia permanens - autosomal dominant +
- ORPHA:99736 Acetazolamide-responsive myotonia - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.644 + (p=5.1E-2) +
+
+
+ Phenotype Score: 0.502 +
+
+
+ Variant Score: 0.944 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.326 to ORPHA:681 Hypokalemic periodic paralysis + +
- Phenotypic similarity 0.307 to ORPHA:682 Hyperkalemic periodic paralysis + +
- Phenotypic similarity 0.266 to OMIM:608390 Myotonia congenita, atypical, acetazolamide-responsive + +
- Phenotypic similarity 0.228 to ORPHA:99736 Acetazolamide-responsive myotonia + +
- Phenotypic similarity 0.193 to ORPHA:684 Paramyotonia congenita of Von Eulenburg + +
- Phenotypic similarity 0.184 to OMIM:613345 Hypokalemic periodic paralysis, type 2 + +
- Phenotypic similarity 0.184 to OMIM:170500 Hyperkalemic periodic paralysis + +
- Phenotypic similarity 0.167 to ORPHA:99735 Myotonia permanens + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 17-63943777-T-C [0/1]
+
+
+ rs754942929
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.944
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SCN4A:ENST00000435607.3:c.3986A>G:p.(Lys1329Arg) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9467736 + +
- REVEL: 0.871 +
- MVP: 0.947 +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0008% +
- ExAC SAS: 0.0246% +
- gnomAD_E_EAS: 0.0058% +
- gnomAD_E_SAS: 0.0228% +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.173 + (p=2.3E-1) +
+
+
+ Phenotype Score: 0.526 +
+
+
+ Variant Score: 0.681 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.526 to OMIM:620369 Congenital myopathy 22B, severe fetal + +
- Phenotypic similarity 0.409 to OMIM:620351 Congenital myopathy 22A, classic + +
- Phenotypic similarity 0.198 to ORPHA:98913 Postsynaptic congenital myasthenic syndromes + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 17-63943777-T-C [0/1]
+
+
+ rs754942929
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.944
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SCN4A:ENST00000435607.3:c.3986A>G:p.(Lys1329Arg) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9467736 + +
- REVEL: 0.871 +
- MVP: 0.947 +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0008% +
- ExAC SAS: 0.0246% +
- gnomAD_E_EAS: 0.0058% +
- gnomAD_E_SAS: 0.0228% +
+
+
+ MISSENSE_VARIANT
+ SNV
+ 17-63940814-G-C [0/1]
+
+
+ rs376833596
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+ LIKELY_BENIGN
+
+
+
+
+ [BP4]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ CONFLICTING_PATHOGENICITY_INTERPRETATIONS
+ (criteria provided, conflicting interpretations)
+
+
+
+ Variant score: 0.417
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SCN4A:ENST00000435607.3:c.5468C>G:p.(Pro1823Arg) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.44369525 + +
- REVEL: 0.242 +
- MVP: 0.444 +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.1874% +
- TOPMed: 0.0159% +
- ExAC AFR: 0.0209% +
- ExAC EAS: 0.2906% +
- ExAC SAS: 0.3627% +
- gnomAD_E_AFR: 0.0200% +
- gnomAD_E_EAS: 0.2990% +
- gnomAD_E_NFE: 0.0009% +
- gnomAD_E_OTH: 0.0747% +
- gnomAD_E_SAS: 0.3349% +
- gnomAD_G_AFR: 0.0115% +
- gnomAD_G_EAS: 0.2466% +
+
+
+
+
+ Other passed variants:
+
+
+
+
+
+ SYNONYMOUS_VARIANT
+ SNV
+ 17-63959349-G-A [0/1]
+
+
+ rs181494727
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ ClinVar:
+
+
+ BENIGN_OR_LIKELY_BENIGN
+
+
+
+
+
+ (criteria provided, multiple submitters, no conflicts)
+
+
+
+ Variant score: 0.091
+
+
+ -
+
- Transcripts: +
- + + SCN4A:ENST00000435607.3:c.1935C>T:p.(=) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0625% +
- TOPMed: 0.0246% +
- ExAC EAS: 0.2670% +
- ExAC SAS: 0.0122% +
- gnomAD_E_EAS: 0.3015% +
- gnomAD_E_NFE: 0.0009% +
- gnomAD_E_OTH: 0.0183% +
- gnomAD_E_SAS: 0.0130% +
- gnomAD_G_EAS: 0.4932% +
+
+
+
+
+
+
+
+ + + ACSS2 + +
+
+
+ Exomiser Score: 0.631 + (p=5.5E-2) +
+
+
+ Phenotype Score: 0.507
+
+
+ Variant Score: 0.932
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Proximity score 0.507 in interactome to PCCB and phenotypic similarity 0.611 to Propionicacidemia associated with PCCB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0002240, Hepatomegaly
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites - HP:0001944, Dehydration
- HP:0010972, Anemia of inadequate production - HP:0001903, Anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001876, Pancytopenia
- HP:0001396, Cholestasis - HP:0002240, Hepatomegaly
- HP:0001410, Decreased liver function - HP:0002240, Hepatomegaly
- HP:0002910, Elevated hepatic transaminase - HP:0003353, Propionyl-CoA carboxylase deficiency
- HP:0001399, Hepatic failure - HP:0002240, Hepatomegaly
- HP:0000938, Osteopenia - HP:0000939, Osteoporosis
- HP:0001642, Pulmonic stenosis - HP:0001638, Cardiomyopathy
- HP:0200114, Metabolic alkalosis - HP:0001942, Metabolic acidosis
- HP:0003073, Hypoalbuminemia - HP:0003353, Propionyl-CoA carboxylase deficiency
- HP:0003233, Decreased HDL cholesterol concentration - HP:0001987, Hyperammonemia
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0001942, Metabolic acidosis
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0003353, Propionyl-CoA carboxylase deficiency
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0003353, Propionyl-CoA carboxylase deficiency
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells - HP:0001875, Neutropenia
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.507 in interactome to PCCB and phenotypic similarity 0.208 to mouse mutant of PCCB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0001914, hemorrhage
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - MP:0003054, spina bifida
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.631 + (p=5.5E-2) +
+
+
+ Phenotype Score: 0.507 +
+
+
+ Variant Score: 0.932 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 20-34926200-G-A [0/1]
+
+
+ rs767041380
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.932
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ACSS2:ENST00000360596.7:c.1822G>A:p.(Gly608Ser) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.93637544 + +
- REVEL: 0.708 +
- MVP: 0.936 +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0015% +
- ExAC SAS: 0.0182% +
- gnomAD_E_OTH: 0.0365% +
- gnomAD_E_SAS: 0.0130% +
+
+
+
+
+
+
+
+ + + THAP11 + +
+
+
+ Exomiser Score: 0.616 + (p=6.1E-2) +
+
+
+ Phenotype Score: 0.576
+
+
+ Variant Score: 0.847
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.576 to mouse mutant involving THAP11.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0002875, decreased erythrocyte cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0002874, decreased hemoglobin content
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function - MP:0005584, abnormal enzyme/coenzyme activity
- HP:0002910, Elevated hepatic transaminase - MP:0005584, abnormal enzyme/coenzyme activity
- HP:0001399, Hepatic failure - MP:0005584, abnormal enzyme/coenzyme activity
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0010499, abnormal ventricle myocardium morphology
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0002874, decreased hemoglobin content
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002874, decreased hemoglobin content
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0005584, abnormal enzyme/coenzyme activity
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0005584, abnormal enzyme/coenzyme activity
- HP:0002366, Abnormal lower motor neuron morphology - MP:0002182, abnormal astrocyte morphology
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0003179, thrombocytopenia
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.207 to zebrafish mutant involving THAP11.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0102283, neuroblast differentiation disrupted, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to USP53 and phenotypic similarity 0.682 to Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss associated with USP53.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001744, Splenomegaly
- HP:0001541, Ascites - HP:0001744, Splenomegaly
- HP:0010972, Anemia of inadequate production - HP:0001744, Splenomegaly
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001744, Splenomegaly
- HP:0001396, Cholestasis - HP:0001396, Cholestasis
- HP:0001410, Decreased liver function - HP:0001396, Cholestasis
- HP:0002910, Elevated hepatic transaminase - HP:0031956, Elevated circulating aspartate aminotransferase concentration
- HP:0001399, Hepatic failure - HP:0001396, Cholestasis
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0410053, Elevated circulating gamma-aminobutyric acid concentration
- HP:0003073, Hypoalbuminemia - HP:0003155, Elevated circulating alkaline phosphatase concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0410053, Elevated circulating gamma-aminobutyric acid concentration
- HP:0001873, Thrombocytopenia - HP:0001744, Splenomegaly
- HP:0002151, Increased serum lactate - HP:0410053, Elevated circulating gamma-aminobutyric acid concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0031956, Elevated circulating aspartate aminotransferase concentration
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001395, Hepatic fibrosis
- HP:0004333, Bone-marrow foam cells - HP:0001744, Splenomegaly
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to USP53 and phenotypic similarity 0.519 to mouse mutant of USP53.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0010124, decreased bone mineral content
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function - MP:0002968, increased circulating alkaline phosphatase level
- HP:0002910, Elevated hepatic transaminase - MP:0002968, increased circulating alkaline phosphatase level
- HP:0001399, Hepatic failure - MP:0002968, increased circulating alkaline phosphatase level
- HP:0000938, Osteopenia - MP:0000063, decreased bone mineral density
- HP:0001642, Pulmonic stenosis - MP:0003896, prolonged PR interval
- HP:0200114, Metabolic alkalosis - MP:0005568, increased circulating total protein level
- HP:0003073, Hypoalbuminemia - MP:0005568, increased circulating total protein level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005178, increased circulating cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005344, increased circulating bilirubin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002968, increased circulating alkaline phosphatase level
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002968, increased circulating alkaline phosphatase level
- HP:0002366, Abnormal lower motor neuron morphology - MP:0004738, abnormal auditory brainstem response
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.616 + (p=6.1E-2) +
+
+
+ Phenotype Score: 0.576 +
+
+
+ Variant Score: 0.847 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_INSERTION
+ INS
+ 16-67842884-G-GCAGCAGCAA [0/1]
+
+
+ rs746671619
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.847
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + THAP11:ENST00000303596.3:c.348_356dup:p.(Gln130_Gln132dup) + + +
- + + THAP11:ENST00000562787.6:c.-492+4516_-492+4517insTTGCTGCTG:p.(=) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_AMR: 0.0060% +
- gnomAD_E_EAS: 0.0296% +
- gnomAD_E_NFE: 0.0019% +
- gnomAD_E_SAS: 0.0033% +
+
+
+
+
+
+
+
+ + + PKD2L1 + +
+
+
+ Exomiser Score: 0.604 + (p=6.5E-2) +
+
+
+ Phenotype Score: 0.519
+
+
+ Variant Score: 0.905
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Proximity score 0.519 in interactome to PKHD1 and phenotypic similarity 0.727 to Caroli disease associated with PKHD1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001974, Leukocytosis
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production - HP:0001974, Leukocytosis
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001974, Leukocytosis
- HP:0001396, Cholestasis - HP:0001396, Cholestasis
- HP:0001410, Decreased liver function - HP:0001409, Portal hypertension
- HP:0002910, Elevated hepatic transaminase - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0001399, Hepatic failure - HP:0001409, Portal hypertension
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001409, Portal hypertension
- HP:0200114, Metabolic alkalosis - HP:0001945, Fever
- HP:0003073, Hypoalbuminemia - HP:0045056, Abnormal circulating alpha-fetoprotein concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0045056, Abnormal circulating alpha-fetoprotein concentration
- HP:0001873, Thrombocytopenia - HP:0001974, Leukocytosis
- HP:0002151, Increased serum lactate - HP:0002908, Conjugated hyperbilirubinemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001394, Cirrhosis
- HP:0004333, Bone-marrow foam cells - HP:0001974, Leukocytosis
- HP:0001531, Failure to thrive in infancy - HP:0001824, Weight loss
- Proximity score 0.519 in interactome to PKHD1 and phenotypic similarity 0.548 to mouse mutant of PKHD1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0003327, liver cyst
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0003254, bile duct inflammation
- HP:0001410, Decreased liver function - MP:0003254, bile duct inflammation
- HP:0002910, Elevated hepatic transaminase - MP:0003254, bile duct inflammation
- HP:0001399, Hepatic failure - MP:0003254, bile duct inflammation
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0003254, bile duct inflammation
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0003254, bile duct inflammation
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0003333, liver fibrosis
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001732, postnatal growth retardation
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.604 + (p=6.5E-2) +
+
+
+ Phenotype Score: 0.519 +
+
+
+ Variant Score: 0.905 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 10-100297029-A-G [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, PP3]
+
+
+
+
+ Variant score: 0.905
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + PKD2L1:ENST00000318222.4:c.1136T>C:p.(Leu379Pro) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9051355 + +
- REVEL: 0.750 +
- MVP: 0.905 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + BUB1B + +
+
+
+ Exomiser Score: 0.597 + (p=6.7E-2) +
+
+
+ Phenotype Score: 0.513
+
+
+ Variant Score: 0.910
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.558 to Mosaic variegated aneuploidy syndrome associated with BUB1B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0006721, Acute lymphoblastic leukemia
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production - HP:0006721, Acute lymphoblastic leukemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0002797, Osteolysis
- HP:0001396, Cholestasis - HP:0000821, Hypothyroidism
- HP:0001410, Decreased liver function - HP:0000821, Hypothyroidism
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0000821, Hypothyroidism
- HP:0000938, Osteopenia - HP:0002797, Osteolysis
- HP:0001642, Pulmonic stenosis - HP:0001682, Subvalvular aortic stenosis
- HP:0200114, Metabolic alkalosis - HP:0010880, Increased nuchal translucency
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0010880, Increased nuchal translucency
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0000821, Hypothyroidism
- HP:0004333, Bone-marrow foam cells - HP:0001679, Abnormal aortic morphology
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.513 to mouse mutant involving BUB1B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0010080, abnormal hepatocyte physiology
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0010080, abnormal hepatocyte physiology
- HP:0001410, Decreased liver function - MP:0010080, abnormal hepatocyte physiology
- HP:0002910, Elevated hepatic transaminase - MP:0010080, abnormal hepatocyte physiology
- HP:0001399, Hepatic failure - MP:0010080, abnormal hepatocyte physiology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0010080, abnormal hepatocyte physiology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0010080, abnormal hepatocyte physiology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0010080, abnormal hepatocyte physiology
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001732, postnatal growth retardation
- PhenIX semantic similarity score: 1.29 (p-value: 0.893820)
-
+
- Known diseases: +
- OMIM:114500 Colorectal cancer, somatic - autosomal dominant +
- OMIM:257300 Mosaic variegated aneuploidy syndrome 1 - autosomal recessive +
- ORPHA:1052 Mosaic variegated aneuploidy syndrome - autosomal recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.597 + (p=6.7E-2) +
+
+
+ Phenotype Score: 0.513 +
+
+
+ Variant Score: 0.910 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 15-40212581-G-T [0/1]
+
+
+ rs2140907754
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, BP4]
+
+
+
+
+ Variant score: 0.910
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + BUB1B:ENST00000287598.11:c.2468G>T:p.(Cys823Phe) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9095185 + +
- REVEL: 0.184 +
- MVP: 0.910 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + ATN1 + +
+
+
+ Exomiser Score: 0.580 + (p=7.3E-2) +
+
+
+ Phenotype Score: 0.558
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.287 to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies associated with ATN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0003186, Inverted nipples
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0010880, Increased nuchal translucency
- HP:0010972, Anemia of inadequate production - HP:0002126, Polymicrogyria
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - HP:0001382, Joint hypermobility
- HP:0001642, Pulmonic stenosis - HP:0001629, Ventricular septal defect
- HP:0200114, Metabolic alkalosis - HP:0010880, Increased nuchal translucency
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0010880, Increased nuchal translucency
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0002126, Polymicrogyria
- HP:0006568, Increased hepatic glycogen content - HP:0003186, Inverted nipples
- HP:0004333, Bone-marrow foam cells - HP:0001680, Coarctation of aorta
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.558 to mouse mutant involving ATN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0002875, decreased erythrocyte cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0002875, decreased erythrocyte cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0005016, decreased lymphocyte cell number
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0000266, abnormal heart morphology
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0005419, decreased circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0001552, increased circulating triglyceride level
- HP:0001873, Thrombocytopenia - MP:0002875, decreased erythrocyte cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0000219, increased neutrophil cell number
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to BMP2 and phenotypic similarity 0.638 to HFE hemochromatosis, modifier of associated with BMP2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001744, Splenomegaly
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production - HP:0001744, Splenomegaly
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0000939, Osteoporosis
- HP:0001396, Cholestasis - HP:0001402, Hepatocellular carcinoma
- HP:0001410, Decreased liver function - HP:0001394, Cirrhosis
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001394, Cirrhosis
- HP:0000938, Osteopenia - HP:0000939, Osteoporosis
- HP:0001642, Pulmonic stenosis - HP:0001640, Cardiomegaly
- HP:0200114, Metabolic alkalosis - HP:0001952, Glucose intolerance
- HP:0003073, Hypoalbuminemia - HP:0003281, Increased circulating ferritin concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003281, Increased circulating ferritin concentration
- HP:0001873, Thrombocytopenia - HP:0001744, Splenomegaly
- HP:0002151, Increased serum lactate - HP:0003281, Increased circulating ferritin concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001394, Cirrhosis
- HP:0004333, Bone-marrow foam cells - HP:0001744, Splenomegaly
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to BMP2 and phenotypic similarity 0.282 to mouse mutant of BMP2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - MP:0000928, incomplete rostral neuropore closure
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.500 in interactome to BMP2 and phenotypic similarity 0.302 to fish mutant of BMP2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - ZP:0009826, liver development decreased process quality, abnormal
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - ZP:0009826, liver development decreased process quality, abnormal
- HP:0001410, Decreased liver function - ZP:0009826, liver development decreased process quality, abnormal
- HP:0002910, Elevated hepatic transaminase - ZP:0009826, liver development decreased process quality, abnormal
- HP:0001399, Hepatic failure - ZP:0009826, liver development decreased process quality, abnormal
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - ZP:0009826, liver development decreased process quality, abnormal
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - ZP:0009826, liver development decreased process quality, abnormal
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - ZP:0009826, liver development decreased process quality, abnormal
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.21 (p-value: 0.919700)
-
+
- Known diseases: +
- OMIM:125370 Dentatorubral-pallidoluysian atrophy - autosomal dominant +
- OMIM:618494 Congenital hypotonia, epilepsy, developmental delay, and digital anomalies - autosomal dominant +
- ORPHA:101 Dentatorubral pallidoluysian atrophy - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.580 + (p=7.3E-2) +
+
+
+ Phenotype Score: 0.558 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.287 to OMIM:618494 Congenital hypotonia, epilepsy, developmental delay, and digital anomalies + +
- Phenotypic similarity 0.138 to ORPHA:101 Dentatorubral pallidoluysian atrophy + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 12-6936728-ACAGCAGCAGCAGCAG-A [0/1]
+
+
+ rs60216939
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ATN1:ENST00000396684.3:c.1494_1508del:p.(Gln498_Gln502del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + PITX3 + +
+
+
+ Exomiser Score: 0.574 + (p=7.5E-2) +
+
+
+ Phenotype Score: 0.662
+
+
+ Variant Score: 0.730
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.662 to mouse mutant involving PITX3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002628, hepatic steatosis
- HP:0001903, Anemia - MP:0003179, thrombocytopenia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0000322, increased granulocyte number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0000221, decreased leukocyte cell number
- HP:0001396, Cholestasis - MP:0002628, hepatic steatosis
- HP:0001410, Decreased liver function - MP:0002628, hepatic steatosis
- HP:0002910, Elevated hepatic transaminase - MP:0002628, hepatic steatosis
- HP:0001399, Hepatic failure - MP:0002628, hepatic steatosis
- HP:0000938, Osteopenia - MP:0004016, decreased bone mass
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0002968, increased circulating alkaline phosphatase level
- HP:0003073, Hypoalbuminemia - MP:0008805, decreased circulating amylase level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005179, decreased circulating cholesterol level
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate - MP:0002968, increased circulating alkaline phosphatase level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0002366, Abnormal lower motor neuron morphology - MP:0011448, decreased dopaminergic neuron number
- HP:0006568, Increased hepatic glycogen content - MP:0002628, hepatic steatosis
- HP:0004333, Bone-marrow foam cells - MP:0000322, increased granulocyte number
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.501 in interactome to MYB and phenotypic similarity 0.628 to mouse mutant of MYB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000691, enlarged spleen
- HP:0001903, Anemia - MP:0001577, anemia
- HP:0001541, Ascites - MP:0000691, enlarged spleen
- HP:0010972, Anemia of inadequate production - MP:0000245, abnormal erythropoiesis
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0002417, abnormal megakaryocyte morphology
- HP:0001396, Cholestasis - MP:0000689, abnormal spleen morphology
- HP:0001410, Decreased liver function - MP:0000689, abnormal spleen morphology
- HP:0002910, Elevated hepatic transaminase - MP:0000689, abnormal spleen morphology
- HP:0001399, Hepatic failure - MP:0000689, abnormal spleen morphology
- HP:0000938, Osteopenia - MP:0002417, abnormal megakaryocyte morphology
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0005505, thrombocytosis
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000689, abnormal spleen morphology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000689, abnormal spleen morphology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000689, abnormal spleen morphology
- HP:0004333, Bone-marrow foam cells - MP:0000222, decreased neutrophil cell number
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to MYB and phenotypic similarity 0.424 to fish mutant of MYB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - ZP:0018768, thymus absent, abnormal
- HP:0001903, Anemia - ZP:0000547, definitive hemopoiesis disrupted, abnormal
- HP:0001541, Ascites - ZP:0001192, heart edematous, abnormal
- HP:0010972, Anemia of inadequate production - ZP:0000547, definitive hemopoiesis disrupted, abnormal
- HP:0005561, Abnormality of bone marrow cell morphology - ZP:0018782, neutrophil differentiation decreased occurrence, abnormal
- HP:0001396, Cholestasis - ZP:0018768, thymus absent, abnormal
- HP:0001410, Decreased liver function - ZP:0018768, thymus absent, abnormal
- HP:0002910, Elevated hepatic transaminase - ZP:0018768, thymus absent, abnormal
- HP:0001399, Hepatic failure - ZP:0018768, thymus absent, abnormal
- HP:0000938, Osteopenia - ZP:0010649, ossification involved in bone maturation arrested, abnormal
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - ZP:0000547, definitive hemopoiesis disrupted, abnormal
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - ZP:0018768, thymus absent, abnormal
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - ZP:0018768, thymus absent, abnormal
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - ZP:0018768, thymus absent, abnormal
- HP:0004333, Bone-marrow foam cells - ZP:0018782, neutrophil differentiation decreased occurrence, abnormal
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.01 (p-value: 0.821160)
-
+
- Known diseases: +
- OMIM:107250 Anterior segment dysgenesis 1, multiple subtypes - autosomal dominant +
- OMIM:610623 Cataract 11, multiple types - autosomal dominant/recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.574 + (p=7.5E-2) +
+
+
+ Phenotype Score: 0.662 +
+
+
+ Variant Score: 0.730 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 10-102231979-C-G [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.730
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + PITX3:ENST00000370002.8:c.102G>C:p.(Lys34Asn) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.73019105 + +
- REVEL: 0.361 +
- MVP: 0.730 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + KCNH6 + +
+
+
+ Exomiser Score: 0.572 + (p=7.5E-2) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.912
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.386 to mouse mutant involving KCNH6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0009176, increased pancreatic alpha cell number
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0009176, increased pancreatic alpha cell number
- HP:0001410, Decreased liver function - MP:0003339, decreased pancreatic beta cell number
- HP:0002910, Elevated hepatic transaminase - MP:0003339, decreased pancreatic beta cell number
- HP:0001399, Hepatic failure - MP:0003339, decreased pancreatic beta cell number
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0002079, increased circulating insulin level
- HP:0003073, Hypoalbuminemia - MP:0002079, increased circulating insulin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002727, decreased circulating insulin level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0002079, increased circulating insulin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0003339, decreased pancreatic beta cell number
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0003339, decreased pancreatic beta cell number
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0003564, abnormal insulin secretion
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.188 to zebrafish mutant involving KCNH6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0000038, pericardium edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - ZP:0005691, dorsal aorta decreased diameter, abnormal
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to KCNE2 and phenotypic similarity 0.227 to Romano-Ward syndrome associated with KCNE2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001279, Syncope
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - HP:0002900, Hypokalemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0002900, Hypokalemia
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0002900, Hypokalemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0012332, Abnormal autonomic nervous system physiology
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to KCNE2 and phenotypic similarity 0.684 to mouse mutant of KCNE2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0008808, decreased spleen iron level
- HP:0001903, Anemia - MP:0001577, anemia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0008388, hypochromic microcytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0008388, hypochromic microcytic anemia
- HP:0001396, Cholestasis - MP:0008006, increased stomach pH
- HP:0001410, Decreased liver function - MP:0008006, increased stomach pH
- HP:0002910, Elevated hepatic transaminase - MP:0008006, increased stomach pH
- HP:0001399, Hepatic failure - MP:0008006, increased stomach pH
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0011285, increased circulating erythropoietin level
- HP:0003073, Hypoalbuminemia - MP:0011891, decreased circulating ferritin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0011891, decreased circulating ferritin level
- HP:0001873, Thrombocytopenia - MP:0005505, thrombocytosis
- HP:0002151, Increased serum lactate - MP:0011285, increased circulating erythropoietin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0008006, increased stomach pH
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0008006, increased stomach pH
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0004139, abnormal gastric parietal cell morphology
- HP:0004333, Bone-marrow foam cells - MP:0001577, anemia
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.572 + (p=7.5E-2) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.912 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 17-63542258-G-T [0/1]
+
+
+ rs764823797
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.912
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + KCNH6:ENST00000314672.10:c.1972G>T:p.(Gly658Trp) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9149335 + +
- REVEL: 0.899 +
- MVP: 0.915 +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0004% +
- ExAC SAS: 0.0182% +
- gnomAD_E_EAS: 0.0058% +
- gnomAD_E_SAS: 0.0227% +
+
+
+
+
+
+
+
+ + + ANXA5 + +
+
+
+ Exomiser Score: 0.572 + (p=7.5E-2) +
+
+
+ Phenotype Score: 0.506
+
+
+ Variant Score: 0.905
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Proximity score 0.506 in interactome to PKD1 and phenotypic similarity 0.362 to Autosomal dominant polycystic kidney disease associated with PKD1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001407, Hepatic cysts
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0001407, Hepatic cysts
- HP:0001410, Decreased liver function - HP:0001407, Hepatic cysts
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001407, Hepatic cysts
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001634, Mitral valve prolapse
- HP:0200114, Metabolic alkalosis - HP:0003259, Elevated circulating creatinine concentration
- HP:0003073, Hypoalbuminemia - HP:0003259, Elevated circulating creatinine concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003259, Elevated circulating creatinine concentration
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0003259, Elevated circulating creatinine concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001407, Hepatic cysts
- HP:0004333, Bone-marrow foam cells - HP:0011004, Abnormal systemic arterial morphology
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.506 in interactome to PKD1 and phenotypic similarity 0.712 to mouse mutant of PKD1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0003327, liver cyst
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0002928, abnormal bile duct morphology
- HP:0001410, Decreased liver function - MP:0003325, decreased liver function
- HP:0002910, Elevated hepatic transaminase - MP:0003325, decreased liver function
- HP:0001399, Hepatic failure - MP:0003325, decreased liver function
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005328, abnormal circulating creatinine level
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005328, abnormal circulating creatinine level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0003325, decreased liver function
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0003325, decreased liver function
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000608, dissociated hepatocytes
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.506 in interactome to PKD1 and phenotypic similarity 0.301 to fish mutant of PKD1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - ZP:0006450, liver cystic, abnormal
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0001192, heart edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - ZP:0006450, liver cystic, abnormal
- HP:0001410, Decreased liver function - ZP:0006450, liver cystic, abnormal
- HP:0002910, Elevated hepatic transaminase - ZP:0006450, liver cystic, abnormal
- HP:0001399, Hepatic failure - ZP:0006450, liver cystic, abnormal
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - ZP:0006450, liver cystic, abnormal
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - ZP:0006450, liver cystic, abnormal
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - ZP:0006450, liver cystic, abnormal
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
-
+
- Known diseases: +
- OMIM:614391 Pregnancy loss, recurrent, susceptibility to, 3 (susceptibility) +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.572 + (p=7.5E-2) +
+
+
+ Phenotype Score: 0.506 +
+
+
+ Variant Score: 0.905 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 4-121678449-C-T [0/1]
+
+
+ rs368943069
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.905
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ANXA5:ENST00000296511.10:c.440G>A:p.(Gly147Glu) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.90547425 + +
- REVEL: 0.490 +
- MVP: 0.905 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + ACVR2A + +
+
+
+ Exomiser Score: 0.549 + (p=8.3E-2) +
+
+
+ Phenotype Score: 0.503
+
+
+ Variant Score: 0.899
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.345 to mouse mutant involving ACVR2A.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0005012, decreased eosinophil cell number
- HP:0001903, Anemia - MP:0000222, decreased neutrophil cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0005012, decreased eosinophil cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0005012, decreased eosinophil cell number
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0000222, decreased neutrophil cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0000222, decreased neutrophil cell number
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.143 to zebrafish mutant involving ACVR2A.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - ZP:0009676, maxilla fused with maxilla, abnormal
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - ZP:0009676, maxilla fused with maxilla, abnormal
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.503 in interactome to BMP6 and phenotypic similarity 0.618 to Symptomatic form of HFE-related hemochromatosis associated with BMP6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001744, Splenomegaly
- HP:0001541, Ascites - HP:0001386, Joint swelling
- HP:0010972, Anemia of inadequate production - HP:0001744, Splenomegaly
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0000939, Osteoporosis
- HP:0001396, Cholestasis - HP:0030153, Cholangiocarcinoma
- HP:0001410, Decreased liver function - HP:0100626, Chronic hepatic failure
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0100626, Chronic hepatic failure
- HP:0000938, Osteopenia - HP:0000939, Osteoporosis
- HP:0001642, Pulmonic stenosis - HP:0001640, Cardiomegaly
- HP:0200114, Metabolic alkalosis - HP:0003074, Hyperglycemia
- HP:0003073, Hypoalbuminemia - HP:0003281, Increased circulating ferritin concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0040171, Decreased serum testosterone concentration
- HP:0001873, Thrombocytopenia - HP:0001744, Splenomegaly
- HP:0002151, Increased serum lactate - HP:0003074, Hyperglycemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0009830, Peripheral neuropathy
- HP:0006568, Increased hepatic glycogen content - HP:0001394, Cirrhosis
- HP:0004333, Bone-marrow foam cells - HP:0001744, Splenomegaly
- HP:0001531, Failure to thrive in infancy - HP:0001824, Weight loss
- Proximity score 0.503 in interactome to BMP6 and phenotypic similarity 0.483 to mouse mutant of BMP6.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000613, abnormal salivary gland morphology
- HP:0001903, Anemia - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0005561, increased mean corpuscular hemoglobin
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0000613, abnormal salivary gland morphology
- HP:0001410, Decreased liver function - MP:0000613, abnormal salivary gland morphology
- HP:0002910, Elevated hepatic transaminase - MP:0000613, abnormal salivary gland morphology
- HP:0001399, Hepatic failure - MP:0000613, abnormal salivary gland morphology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0005333, decreased heart rate
- HP:0200114, Metabolic alkalosis - MP:0005343, increased circulating aspartate transaminase level
- HP:0003073, Hypoalbuminemia - MP:0002941, increased circulating alanine transaminase level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002941, increased circulating alanine transaminase level
- HP:0001873, Thrombocytopenia - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0002151, Increased serum lactate - MP:0005343, increased circulating aspartate transaminase level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000613, abnormal salivary gland morphology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000613, abnormal salivary gland morphology
- HP:0002366, Abnormal lower motor neuron morphology - MP:0002152, abnormal brain morphology
- HP:0006568, Increased hepatic glycogen content - MP:0000613, abnormal salivary gland morphology
- HP:0004333, Bone-marrow foam cells - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.549 + (p=8.3E-2) +
+
+
+ Phenotype Score: 0.503 +
+
+
+ Variant Score: 0.899 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 2-147927261-A-T [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.899
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ACVR2A:ENST00000241416.12:c.1529A>T:p.(Glu510Val) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8990258 + +
- REVEL: 0.526 +
- MVP: 0.899 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + MME + +
+
+
+ Exomiser Score: 0.541 + (p=8.5E-2) +
+
+
+ Phenotype Score: 0.510
+
+
+ Variant Score: 0.888
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.232 to Spinocerebellar ataxia type 43 associated with MME.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0003387, Decreased number of large peripheral myelinated nerve fibers
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0003387, Decreased number of large peripheral myelinated nerve fibers
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.424 to mouse mutant involving MME.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0005151, diffuse hepatic necrosis
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0005151, diffuse hepatic necrosis
- HP:0001410, Decreased liver function - MP:0005151, diffuse hepatic necrosis
- HP:0002910, Elevated hepatic transaminase - MP:0005151, diffuse hepatic necrosis
- HP:0001399, Hepatic failure - MP:0005151, diffuse hepatic necrosis
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0005416, abnormal circulating protein level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005416, abnormal circulating protein level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0005151, diffuse hepatic necrosis
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0005151, diffuse hepatic necrosis
- HP:0002366, Abnormal lower motor neuron morphology - MP:0005404, abnormal axon morphology
- HP:0006568, Increased hepatic glycogen content - MP:0005151, diffuse hepatic necrosis
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.510 in interactome to CR2 and phenotypic similarity 0.667 to Common variable immunodeficiency associated with CR2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001878, Hemolytic anemia
- HP:0001541, Ascites - HP:0001744, Splenomegaly
- HP:0010972, Anemia of inadequate production - HP:0001878, Hemolytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001888, Lymphopenia
- HP:0001396, Cholestasis - HP:0001392, Abnormality of the liver
- HP:0001410, Decreased liver function - HP:0001392, Abnormality of the liver
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001392, Abnormality of the liver
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0000979, Purpura
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0001973, Autoimmune thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001392, Abnormality of the liver
- HP:0004333, Bone-marrow foam cells - HP:0001888, Lymphopenia
- HP:0001531, Failure to thrive in infancy - HP:0001531, Failure to thrive in infancy
- Proximity score 0.510 in interactome to CR2 and phenotypic similarity 0.362 to mouse mutant of CR2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002359, abnormal spleen germinal center morphology
- HP:0001903, Anemia - MP:0000222, decreased neutrophil cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0004940, abnormal B-1 B cell morphology
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0004940, abnormal B-1 B cell morphology
- HP:0001396, Cholestasis - MP:0002359, abnormal spleen germinal center morphology
- HP:0001410, Decreased liver function - MP:0002359, abnormal spleen germinal center morphology
- HP:0002910, Elevated hepatic transaminase - MP:0002359, abnormal spleen germinal center morphology
- HP:0001399, Hepatic failure - MP:0002359, abnormal spleen germinal center morphology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0000222, decreased neutrophil cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002359, abnormal spleen germinal center morphology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002359, abnormal spleen germinal center morphology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0002359, abnormal spleen germinal center morphology
- HP:0004333, Bone-marrow foam cells - MP:0000222, decreased neutrophil cell number
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.13 (p-value: 0.999760)
-
+
- Known diseases: +
- OMIM:617017 Charcot-Marie-Tooth disease, axonal, type 2T - autosomal dominant/recessive +
- OMIM:617018 ?Spinocerebellar ataxia 43 (unconfirmed) +
- ORPHA:497764 Spinocerebellar ataxia type 43 - autosomal dominant/recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.541 + (p=8.5E-2) +
+
+
+ Phenotype Score: 0.510 +
+
+
+ Variant Score: 0.888 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.232 to ORPHA:497764 Spinocerebellar ataxia type 43 + +
- Phenotypic similarity 0.183 to OMIM:617018 ?Spinocerebellar ataxia 43 + +
- Phenotypic similarity 0.183 to OMIM:617017 Charcot-Marie-Tooth disease, axonal, type 2T + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 3-155116718-A-G [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.888
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + MME:ENST00000360490.7:c.494A>G:p.(Tyr165Cys) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8877893 + +
- REVEL: 0.514 +
- MVP: 0.888 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + SLC7A10 + +
+
+
+ Exomiser Score: 0.538 + (p=8.6E-2) +
+
+
+ Phenotype Score: 0.502
+
+
+ Variant Score: 0.895
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.265 to mouse mutant involving SLC7A10.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.502 in interactome to SLC7A7 and phenotypic similarity 0.789 to Lysinuric protein intolerance associated with SLC7A7.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001433, Hepatosplenomegaly
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001903, Anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0031020, Bone marrow hypercellularity
- HP:0001396, Cholestasis - HP:0001399, Hepatic failure
- HP:0001410, Decreased liver function - HP:0001399, Hepatic failure
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001399, Hepatic failure
- HP:0000938, Osteopenia - HP:0000938, Osteopenia
- HP:0001642, Pulmonic stenosis - HP:0001627, Abnormal heart morphology
- HP:0200114, Metabolic alkalosis - HP:0001987, Hyperammonemia
- HP:0003073, Hypoalbuminemia - HP:0003281, Increased circulating ferritin concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003233, Decreased HDL cholesterol concentration
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0003348, Hyperalaninemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0012280, Hepatic amyloidosis
- HP:0004333, Bone-marrow foam cells - HP:0012156, Hemophagocytosis
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.502 in interactome to SLC7A7 and phenotypic similarity 0.519 to mouse mutant of SLC7A7.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0004953, decreased spleen weight
- HP:0001903, Anemia - MP:0000219, increased neutrophil cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0000219, increased neutrophil cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0005016, decreased lymphocyte cell number
- HP:0001396, Cholestasis - MP:0000597, delayed hepatic development
- HP:0001410, Decreased liver function - MP:0000597, delayed hepatic development
- HP:0002910, Elevated hepatic transaminase - MP:0000597, delayed hepatic development
- HP:0001399, Hepatic failure - MP:0000597, delayed hepatic development
- HP:0000938, Osteopenia - MP:0020137, decreased bone mineralization
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0000219, increased neutrophil cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000597, delayed hepatic development
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000597, delayed hepatic development
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000597, delayed hepatic development
- HP:0004333, Bone-marrow foam cells - MP:0000219, increased neutrophil cell number
- HP:0001531, Failure to thrive in infancy - MP:0008489, slow postnatal weight gain
- Proximity score 0.502 in interactome to SLC7A7 and phenotypic similarity 0.323 to fish mutant of SLC7A7.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - ZP:0016849, microglia development decreased occurrence, abnormal
- HP:0001903, Anemia - ZP:0016849, microglia development decreased occurrence, abnormal
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - ZP:0016849, microglia development decreased occurrence, abnormal
- HP:0005561, Abnormality of bone marrow cell morphology - ZP:0016849, microglia development decreased occurrence, abnormal
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - ZP:0016849, microglia development decreased occurrence, abnormal
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0016849, microglia development decreased occurrence, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - ZP:0016849, microglia development decreased occurrence, abnormal
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.538 + (p=8.6E-2) +
+
+
+ Phenotype Score: 0.502 +
+
+
+ Variant Score: 0.895 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 19-33215803-C-T [0/1]
+
+
+ rs567938130
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.895
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SLC7A10:ENST00000253188.8:c.322G>A:p.(Ala108Thr) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9017956 + +
- REVEL: 0.401 +
- MVP: 0.902 +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0312% +
- TOPMed: 0.0110% +
- ExAC NFE: 0.0535% +
- ExAC SAS: 0.0247% +
- gnomAD_E_AMR: 0.0112% +
- gnomAD_E_EAS: 0.0162% +
- gnomAD_E_NFE: 0.0056% +
- gnomAD_E_SAS: 0.0164% +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.395 + (p=1.3E-1) +
+
+
+ Phenotype Score: 0.502 +
+
+
+ Variant Score: 0.832 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 19-33215803-C-T [0/1]
+
+
+ rs567938130
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.895
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SLC7A10:ENST00000253188.8:c.322G>A:p.(Ala108Thr) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.9017956 + +
- REVEL: 0.401 +
- MVP: 0.902 +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0312% +
- TOPMed: 0.0110% +
- ExAC NFE: 0.0535% +
- ExAC SAS: 0.0247% +
- gnomAD_E_AMR: 0.0112% +
- gnomAD_E_EAS: 0.0162% +
- gnomAD_E_NFE: 0.0056% +
- gnomAD_E_SAS: 0.0164% +
+
+
+ SPLICE_REGION_VARIANT
+ SNV
+ 19-33210906-T-C [0/1]
+
+
+ rs375747229
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.770
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SLC7A10:ENST00000253188.8:c.1017-8A>G:p.? + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0625% +
- TOPMed: 0.0068% +
- ExAC AFR: 0.0108% +
- ExAC EAS: 0.2005% +
- ExAC SAS: 0.0621% +
- gnomAD_E_EAS: 0.1803% +
- gnomAD_E_OTH: 0.0184% +
- gnomAD_E_SAS: 0.0455% +
- gnomAD_G_EAS: 0.2469% +
+
+
+
+
+
+
+
+ + + ZNF787 + +
+
+
+ Exomiser Score: 0.526 + (p=9.0E-2) +
+
+
+ Phenotype Score: 0.537
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.537 to mouse mutant involving ZNF787.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002833, increased heart weight
- HP:0001903, Anemia - MP:0003179, thrombocytopenia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0003179, thrombocytopenia
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0002833, increased heart weight
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0000186, decreased circulating HDL cholesterol level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000186, decreased circulating HDL cholesterol level
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0005293, impaired glucose tolerance
- HP:0004333, Bone-marrow foam cells - MP:0003179, thrombocytopenia
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.526 + (p=9.0E-2) +
+
+
+ Phenotype Score: 0.537 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_INSERTION
+ INS
+ 19-56088071-C-CTCG [0/1]
+
+
+ rs5828672
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ZNF787:ENST00000610935.2:c.1098_1100dup:p.(Asp366dup) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + PDE6B + +
+
+
+ Exomiser Score: 0.522 + (p=9.1E-2) +
+
+
+ Phenotype Score: 0.503
+
+
+ Variant Score: 0.887
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.317 to Retinitis pigmentosa associated with PDE6B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0000842, Hyperinsulinemia
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0000135, Hypogonadism
- HP:0001410, Decreased liver function - HP:0000135, Hypogonadism
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0000135, Hypogonadism
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0000842, Hyperinsulinemia
- HP:0003073, Hypoalbuminemia - HP:0000842, Hyperinsulinemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0000842, Hyperinsulinemia
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0000842, Hyperinsulinemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0000648, Optic atrophy
- HP:0006568, Increased hepatic glycogen content - HP:0005978, Type II diabetes mellitus
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - HP:0001513, Obesity
- Phenotypic similarity 0.460 to mouse mutant involving PDE6B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0012311, decreased defecation amount
- HP:0001410, Decreased liver function - MP:0012311, decreased defecation amount
- HP:0002910, Elevated hepatic transaminase - MP:0012311, decreased defecation amount
- HP:0001399, Hepatic failure - MP:0012311, decreased defecation amount
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005627, increased circulating potassium level
- HP:0003073, Hypoalbuminemia - MP:0008805, decreased circulating amylase level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002644, decreased circulating triglyceride level
- HP:0001873, Thrombocytopenia - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0002151, Increased serum lactate - MP:0005627, increased circulating potassium level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0012311, decreased defecation amount
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0012311, decreased defecation amount
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.503 in interactome to ENTPD5 and phenotypic similarity 0.690 to mouse mutant of ENTPD5.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000599, enlarged liver
- HP:0001903, Anemia - MP:0008114, abnormal Kupffer cell morphology
- HP:0001541, Ascites - MP:0000599, enlarged liver
- HP:0010972, Anemia of inadequate production - MP:0008114, abnormal Kupffer cell morphology
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0008114, abnormal Kupffer cell morphology
- HP:0001396, Cholestasis - MP:0010042, abnormal oval cell physiology
- HP:0001410, Decreased liver function - MP:0010042, abnormal oval cell physiology
- HP:0002910, Elevated hepatic transaminase - MP:0010042, abnormal oval cell physiology
- HP:0001399, Hepatic failure - MP:0010042, abnormal oval cell physiology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0002968, increased circulating alkaline phosphatase level
- HP:0003073, Hypoalbuminemia - MP:0005419, decreased circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0003983, decreased cholesterol level
- HP:0001873, Thrombocytopenia - MP:0008114, abnormal Kupffer cell morphology
- HP:0002151, Increased serum lactate - MP:0005344, increased circulating bilirubin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0010042, abnormal oval cell physiology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0010042, abnormal oval cell physiology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000607, abnormal hepatocyte morphology
- HP:0004333, Bone-marrow foam cells - MP:0008114, abnormal Kupffer cell morphology
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.503 in interactome to ENTPD5 and phenotypic similarity 0.324 to fish mutant of ENTPD5.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - ZP:0002797, bone mineralization disrupted, abnormal
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - ZP:0002797, bone mineralization disrupted, abnormal
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - ZP:0009437, phosphate ion homeostasis disrupted, abnormal
- HP:0003073, Hypoalbuminemia - ZP:0009437, phosphate ion homeostasis disrupted, abnormal
- HP:0003233, Decreased HDL cholesterol concentration - ZP:0009437, phosphate ion homeostasis disrupted, abnormal
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - ZP:0009437, phosphate ion homeostasis disrupted, abnormal
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - ZP:0009437, phosphate ion homeostasis disrupted, abnormal
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.26 (p-value: 0.997250)
-
+
- Known diseases: +
- OMIM:163500 Night blindness, congenital stationary, autosomal dominant 2 - autosomal dominant +
- OMIM:613801 Retinitis pigmentosa-40 - autosomal recessive +
- ORPHA:215 Congenital stationary night blindness - autosomal dominant +
- ORPHA:791 Retinitis pigmentosa - autosomal recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.522 + (p=9.1E-2) +
+
+
+ Phenotype Score: 0.503 +
+
+
+ Variant Score: 0.887 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 4-662556-G-A [0/1]
+
+
+ rs369416193
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.887
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + PDE6B:ENST00000496514.6:c.1770G>A:p.(Met590Ile) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8875141 + +
- REVEL: 0.805 +
- MVP: 0.888 +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_AMR: 0.0030% +
+
+
+
+
+
+
+
+ + + CACNA1G + +
+
+
+ Exomiser Score: 0.516 + (p=9.3E-2) +
+
+
+ Phenotype Score: 0.502
+
+
+ Variant Score: 0.886
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.225 to mouse mutant involving CACNA1G.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0003354, astrocytosis
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - MP:0000876, Purkinje cell degeneration
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.502 in interactome to CACNA1D and phenotypic similarity 0.618 to Primary hyperaldosteronism-seizures-neurological abnormalities syndrome associated with CACNA1D.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0008221, Adrenal hyperplasia
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0008221, Adrenal hyperplasia
- HP:0001410, Decreased liver function - HP:0000859, Hyperaldosteronism
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0000859, Hyperaldosteronism
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001714, Ventricular hypertrophy
- HP:0200114, Metabolic alkalosis - HP:0200114, Metabolic alkalosis
- HP:0003073, Hypoalbuminemia - HP:0040084, Abnormal circulating renin
- HP:0003233, Decreased HDL cholesterol concentration - HP:0000859, Hyperaldosteronism
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0200114, Metabolic alkalosis
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0008221, Adrenal hyperplasia
- HP:0004333, Bone-marrow foam cells - HP:0002170, Intracranial hemorrhage
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.502 in interactome to CACNA1D and phenotypic similarity 0.423 to mouse mutant of CACNA1D.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0009176, increased pancreatic alpha cell number
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0009175, abnormal pancreatic beta cell differentiation
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0005215, abnormal pancreatic islet morphology
- HP:0001410, Decreased liver function - MP:0003339, decreased pancreatic beta cell number
- HP:0002910, Elevated hepatic transaminase - MP:0003339, decreased pancreatic beta cell number
- HP:0001399, Hepatic failure - MP:0003339, decreased pancreatic beta cell number
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0004231, abnormal calcium ion homeostasis
- HP:0003073, Hypoalbuminemia - MP:0002727, decreased circulating insulin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002727, decreased circulating insulin level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0004231, abnormal calcium ion homeostasis
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0003339, decreased pancreatic beta cell number
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0003339, decreased pancreatic beta cell number
- HP:0002366, Abnormal lower motor neuron morphology - MP:0004434, abnormal cochlear outer hair cell physiology
- HP:0006568, Increased hepatic glycogen content - MP:0009175, abnormal pancreatic beta cell differentiation
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.502 in interactome to CACNA1D and phenotypic similarity 0.192 to fish mutant of CACNA1D.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0011236, ribbon synapse neuromast hair cell morphology, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.47 (p-value: 0.999670)
-
+
- Known diseases: +
- OMIM:616795 Spinocerebellar ataxia 42 - autosomal dominant +
- OMIM:618087 Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits - autosomal dominant +
- ORPHA:458803 Spinocerebellar ataxia type 42 - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.516 + (p=9.3E-2) +
+
+
+ Phenotype Score: 0.502 +
+
+
+ Variant Score: 0.886 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 17-50578553-T-C [0/1]
+
+
+ rs1199012971
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3]
+
+
+
+
+ Variant score: 0.886
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + CACNA1G:ENST00000359106.10:c.2290T>C:p.(Tyr764His) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8858178 + +
- REVEL: 0.695 +
- MVP: 0.886 +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_NFE: 0.0011% +
+
+
+
+
+
+
+
+ + + SLC7A11 + +
+
+
+ Exomiser Score: 0.512 + (p=9.5E-2) +
+
+
+ Phenotype Score: 0.503
+
+
+ Variant Score: 0.883
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.318 to mouse mutant involving SLC7A11.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0004725, decreased platelet serotonin level
- HP:0001541, Ascites - MP:0005606, increased bleeding time
- HP:0010972, Anemia of inadequate production - MP:0004725, decreased platelet serotonin level
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0005606, increased bleeding time
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0004725, decreased platelet serotonin level
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0004725, decreased platelet serotonin level
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.503 in interactome to TNFSF11 and phenotypic similarity 0.548 to Osteopetrosis, autosomal recessive 2 associated with TNFSF11.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001433, Hepatosplenomegaly
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites - HP:0001433, Hepatosplenomegaly
- HP:0010972, Anemia of inadequate production - HP:0001978, Extramedullary hematopoiesis
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001876, Pancytopenia
- HP:0001396, Cholestasis - HP:0001433, Hepatosplenomegaly
- HP:0001410, Decreased liver function - HP:0001433, Hepatosplenomegaly
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001433, Hepatosplenomegaly
- HP:0000938, Osteopenia - HP:0011002, Osteopetrosis
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0001293, Cranial nerve compression
- HP:0006568, Increased hepatic glycogen content - HP:0001433, Hepatosplenomegaly
- HP:0004333, Bone-marrow foam cells - HP:0001876, Pancytopenia
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.503 in interactome to TNFSF11 and phenotypic similarity 0.690 to mouse mutant of TNFSF11.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0004952, increased spleen weight
- HP:0001903, Anemia - MP:0002811, macrocytic anemia
- HP:0001541, Ascites - MP:0010249, lactation failure
- HP:0010972, Anemia of inadequate production - MP:0002811, macrocytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0004985, decreased osteoclast cell number
- HP:0001396, Cholestasis - MP:0001823, thymus hypoplasia
- HP:0001410, Decreased liver function - MP:0010249, lactation failure
- HP:0002910, Elevated hepatic transaminase - MP:0010249, lactation failure
- HP:0001399, Hepatic failure - MP:0010249, lactation failure
- HP:0000938, Osteopenia - MP:0000062, increased bone mineral density
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0004985, decreased osteoclast cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0010249, lactation failure
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0010249, lactation failure
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0001823, thymus hypoplasia
- HP:0004333, Bone-marrow foam cells - MP:0004985, decreased osteoclast cell number
- HP:0001531, Failure to thrive in infancy - MP:0001732, postnatal growth retardation
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.512 + (p=9.5E-2) +
+
+
+ Phenotype Score: 0.503 +
+
+
+ Variant Score: 0.883 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 4-138214610-T-C [0/1]
+
+
+ rs35186416
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+
+ Variant score: 0.883
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SLC7A11:ENST00000280612.9:c.766A>G:p.(Thr256Ala) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.883 + +
- REVEL: 0.883 +
- MVP: 0.881 +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0004% +
+
+
+
+
+
+
+
+ + + ITPR1 + +
+
+
+ Exomiser Score: 0.501 + (p=9.8E-2) +
+
+
+ Phenotype Score: 0.507
+
+
+ Variant Score: 0.874
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.168 to Gillespie syndrome associated with ITPR1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - HP:0001660, Truncus arteriosus
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.254 to mouse mutant involving ITPR1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0003059, decreased insulin secretion
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0003059, decreased insulin secretion
- HP:0001410, Decreased liver function - MP:0003059, decreased insulin secretion
- HP:0002910, Elevated hepatic transaminase - MP:0003059, decreased insulin secretion
- HP:0001399, Hepatic failure - MP:0003059, decreased insulin secretion
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0003059, decreased insulin secretion
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0003059, decreased insulin secretion
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0003059, decreased insulin secretion
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.507 in interactome to STIM1 and phenotypic similarity 0.546 to Stormorken syndrome associated with STIM1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0006270, Hypoplastic spleen
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0001903, Anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001903, Anemia
- HP:0001396, Cholestasis - HP:0001746, Asplenia
- HP:0001410, Decreased liver function - HP:0001746, Asplenia
- HP:0002910, Elevated hepatic transaminase - HP:0025435, Increased circulating lactate dehydrogenase concentration
- HP:0001399, Hepatic failure - HP:0001746, Asplenia
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001892, Abnormal bleeding
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0025435, Increased circulating lactate dehydrogenase concentration
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0025435, Increased circulating lactate dehydrogenase concentration
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001746, Asplenia
- HP:0004333, Bone-marrow foam cells - HP:0001903, Anemia
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.507 in interactome to STIM1 and phenotypic similarity 0.630 to mouse mutant of STIM1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000691, enlarged spleen
- HP:0001903, Anemia - MP:0003179, thrombocytopenia
- HP:0001541, Ascites - MP:0005048, abnormal thrombosis
- HP:0010972, Anemia of inadequate production - MP:0000228, abnormal thrombopoiesis
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0011747, myelofibrosis
- HP:0001396, Cholestasis - MP:0008476, increased spleen red pulp amount
- HP:0001410, Decreased liver function - MP:0008476, increased spleen red pulp amount
- HP:0002910, Elevated hepatic transaminase - MP:0008476, increased spleen red pulp amount
- HP:0001399, Hepatic failure - MP:0008476, increased spleen red pulp amount
- HP:0000938, Osteopenia - MP:0002397, abnormal bone marrow morphology
- HP:0001642, Pulmonic stenosis - MP:0005606, increased bleeding time
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0008476, increased spleen red pulp amount
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0008476, increased spleen red pulp amount
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0008476, increased spleen red pulp amount
- HP:0004333, Bone-marrow foam cells - MP:0011747, myelofibrosis
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.507 in interactome to STIM1 and phenotypic similarity 0.182 to fish mutant of STIM1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0138468, CaP motoneuron decreased occurrence axon guidance, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - ZP:0138469, CaP motoneuron arrested axon extension involved in axon guidance, abnormal
- PhenIX semantic similarity score: 0.09 (p-value: 0.999560)
-
+
- Known diseases: +
- OMIM:117360 Spinocerebellar ataxia 29, congenital nonprogressive - autosomal dominant +
- OMIM:206700 Gillespie syndrome - autosomal dominant/recessive +
- OMIM:606658 Spinocerebellar ataxia 15 - autosomal dominant +
- ORPHA:1065 Aniridia-cerebellar ataxia-intellectual disability syndrome - autosomal dominant/recessive +
- ORPHA:208513 Spinocerebellar ataxia type 29 - autosomal dominant +
- ORPHA:98769 Spinocerebellar ataxia type 15/16 - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.501 + (p=9.8E-2) +
+
+
+ Phenotype Score: 0.507 +
+
+
+ Variant Score: 0.874 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.168 to OMIM:206700 Gillespie syndrome + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 3-4669692-A-G [0/1]
+
+
+ rs1389594446
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.874
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ITPR1:ENST00000649015.2:c.1925A>G:p.(Asn642Ser) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.87393194 + +
- REVEL: 0.427 +
- MVP: 0.874 +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_NFE: 0.0009% +
+
+
+
+
+
+
+
+ + + TMPRSS9 + +
+
+
+ Exomiser Score: 0.489 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.876
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.213 to mouse mutant involving TMPRSS9.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001260, increased body weight
- Proximity score 0.500 in interactome to SLC25A13 and phenotypic similarity 0.769 to Neonatal intrahepatic cholestasis due to citrin deficiency associated with SLC25A13.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001433, Hepatosplenomegaly
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001903, Anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001903, Anemia
- HP:0001396, Cholestasis - HP:0001396, Cholestasis
- HP:0001410, Decreased liver function - HP:0001396, Cholestasis
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001396, Cholestasis
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001892, Abnormal bleeding
- HP:0200114, Metabolic alkalosis - HP:0001987, Hyperammonemia
- HP:0003073, Hypoalbuminemia - HP:0003073, Hypoalbuminemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003233, Decreased HDL cholesterol concentration
- HP:0001873, Thrombocytopenia - HP:0001903, Anemia
- HP:0002151, Increased serum lactate - HP:0003128, Lactic acidosis
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001397, Hepatic steatosis
- HP:0004333, Bone-marrow foam cells - HP:0001903, Anemia
- HP:0001531, Failure to thrive in infancy - HP:0001531, Failure to thrive in infancy
- Proximity score 0.500 in interactome to SLC25A13 and phenotypic similarity 0.461 to mouse mutant of SLC25A13.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002628, hepatic steatosis
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0009355, increased liver triglyceride level
- HP:0001410, Decreased liver function - MP:0009355, increased liver triglyceride level
- HP:0002910, Elevated hepatic transaminase - MP:0009355, increased liver triglyceride level
- HP:0001399, Hepatic failure - MP:0009355, increased liver triglyceride level
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0002727, decreased circulating insulin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002727, decreased circulating insulin level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0009355, increased liver triglyceride level
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0009355, increased liver triglyceride level
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0002628, hepatic steatosis
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.489 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.876 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 19-2425144-G-A [0/1]
+
+
+ rs536020211
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.876
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + TMPRSS9:ENST00000696167.1:c.2860G>A:p.(Glu954Lys) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.885597 + +
- REVEL: 0.636 +
- MVP: 0.886 +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0625% +
- TOPMed: 0.0625% +
- ExAC EAS: 0.0773% +
- ExAC SAS: 0.0091% +
- gnomAD_E_EAS: 0.0248% +
- gnomAD_E_SAS: 0.0105% +
+
+
+
+
+
+
+
+ + + MTOR + +
+
+
+ Exomiser Score: 0.486 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.509
+
+
+ Variant Score: 0.865
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.477 to Smith-Kingsmore syndrome associated with MTOR.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001873, Thrombocytopenia
- HP:0001903, Anemia - HP:0001873, Thrombocytopenia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0001873, Thrombocytopenia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001873, Thrombocytopenia
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0001943, Hypoglycemia
- HP:0003073, Hypoalbuminemia - HP:0001943, Hypoglycemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0001943, Hypoglycemia
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0001943, Hypoglycemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0012650, Perisylvian polymicrogyria
- HP:0006568, Increased hepatic glycogen content - HP:0001943, Hypoglycemia
- HP:0004333, Bone-marrow foam cells - HP:0001873, Thrombocytopenia
- HP:0001531, Failure to thrive in infancy - HP:0001520, Large for gestational age
- Phenotypic similarity 0.460 to mouse mutant involving MTOR.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0005561, increased mean corpuscular hemoglobin
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0005561, increased mean corpuscular hemoglobin
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0005561, increased mean corpuscular hemoglobin
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000183, decreased circulating LDL cholesterol level
- HP:0001873, Thrombocytopenia - MP:0005561, increased mean corpuscular hemoglobin
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0005561, increased mean corpuscular hemoglobin
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.394 to zebrafish mutant involving MTOR.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - ZP:0000720, liver decreased size, abnormal
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - ZP:0015598, liver low brightness, abnormal
- HP:0001410, Decreased liver function - ZP:0015598, liver low brightness, abnormal
- HP:0002910, Elevated hepatic transaminase - ZP:0015598, liver low brightness, abnormal
- HP:0001399, Hepatic failure - ZP:0015598, liver low brightness, abnormal
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - ZP:0021359, whole organism decreased occurrence cholesterol biosynthetic process, abnormal
- HP:0003073, Hypoalbuminemia - ZP:0021359, whole organism decreased occurrence cholesterol biosynthetic process, abnormal
- HP:0003233, Decreased HDL cholesterol concentration - ZP:0021359, whole organism decreased occurrence cholesterol biosynthetic process, abnormal
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - ZP:0021359, whole organism decreased occurrence cholesterol biosynthetic process, abnormal
- HP:0031964, Elevated circulating alanine aminotransferase concentration - ZP:0015598, liver low brightness, abnormal
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - ZP:0015598, liver low brightness, abnormal
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0021361, myelin sheath spinal cord decreased thickness, abnormal
- HP:0006568, Increased hepatic glycogen content - ZP:0000720, liver decreased size, abnormal
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.509 in interactome to MEFV and phenotypic similarity 0.588 to Familial Mediterranean fever associated with MEFV.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0002716, Lymphadenopathy
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production - HP:0002716, Lymphadenopathy
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0002716, Lymphadenopathy
- HP:0001396, Cholestasis - HP:0006554, Acute hepatic failure
- HP:0001410, Decreased liver function - HP:0006554, Acute hepatic failure
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0006554, Acute hepatic failure
- HP:0000938, Osteopenia - HP:0001369, Arthritis
- HP:0001642, Pulmonic stenosis - HP:0001658, Myocardial infarction
- HP:0200114, Metabolic alkalosis - HP:0001945, Fever
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0002716, Lymphadenopathy
- HP:0002151, Increased serum lactate - HP:0001945, Fever
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0006554, Acute hepatic failure
- HP:0004333, Bone-marrow foam cells - HP:0002633, Vasculitis
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.509 in interactome to MEFV and phenotypic similarity 0.616 to mouse mutant of MEFV.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000691, enlarged spleen
- HP:0001903, Anemia - MP:0001577, anemia
- HP:0001541, Ascites - MP:0000691, enlarged spleen
- HP:0010972, Anemia of inadequate production - MP:0001577, anemia
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0000218, increased leukocyte cell number
- HP:0001396, Cholestasis - MP:0001860, liver inflammation
- HP:0001410, Decreased liver function - MP:0001860, liver inflammation
- HP:0002910, Elevated hepatic transaminase - MP:0001860, liver inflammation
- HP:0001399, Hepatic failure - MP:0001860, liver inflammation
- HP:0000938, Osteopenia - MP:0002933, joint inflammation
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0008553, increased circulating tumor necrosis factor level
- HP:0003073, Hypoalbuminemia - MP:0008553, increased circulating tumor necrosis factor level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0008553, increased circulating tumor necrosis factor level
- HP:0001873, Thrombocytopenia - MP:0000322, increased granulocyte number
- HP:0002151, Increased serum lactate - MP:0008553, increased circulating tumor necrosis factor level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0001860, liver inflammation
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0001860, liver inflammation
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0001860, liver inflammation
- HP:0004333, Bone-marrow foam cells - MP:0005425, increased macrophage cell number
- HP:0001531, Failure to thrive in infancy - MP:0001732, postnatal growth retardation
- PhenIX semantic similarity score: 0.87 (p-value: 0.850660)
-
+
- Known diseases: +
- OMIM:607341 Focal cortical dysplasia, type II, somatic - somatic +
- OMIM:616638 Smith-Kingsmore syndrome - autosomal dominant +
- ORPHA:457485 Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.486 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.509 +
+
+
+ Variant Score: 0.865 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.477 to OMIM:616638 Smith-Kingsmore syndrome + +
- Phenotypic similarity 0.292 to ORPHA:457485 Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 1-11199603-C-A [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, PP3]
+
+
+
+
+ Variant score: 0.865
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + MTOR:ENST00000361445.9:c.4045G>T:p.(Asp1349Tyr) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.86453384 + +
- REVEL: 0.644 +
- MVP: 0.865 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + TYW1B + +
+
+
+ Exomiser Score: 0.483 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.565
+
+
+ Variant Score: 0.800
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.565 to mouse mutant involving TYW1B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0000208, decreased hematocrit
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0000208, decreased hematocrit
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0002910, Elevated hepatic transaminase - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0001399, Hepatic failure - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0005419, decreased circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005419, decreased circulating serum albumin level
- HP:0001873, Thrombocytopenia - MP:0000208, decreased hematocrit
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002966, decreased circulating alkaline phosphatase level
- HP:0002366, Abnormal lower motor neuron morphology - MP:0006243, impaired pupillary reflex
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.483 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.565 +
+
+
+ Variant Score: 0.800 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ SPLICE_REGION_VARIANT
+ SNV
+ 7-72629004-C-T [0/1]
+
+
+ rs782670276
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.800
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + TYW1B:ENST00000620995.5:c.1507-7G>A:p.? + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0004% +
+
+
+
+
+
+
+
+ + + SLC25A31 + +
+
+
+ Exomiser Score: 0.482 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.501
+
+
+ Variant Score: 0.872
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.124 to mouse mutant involving SLC25A31.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0014052, increased male germ cell apoptosis
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to SLC25A4 and phenotypic similarity 0.609 to Autosomal dominant progressive external ophthalmoplegia associated with SLC25A4.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001392, Abnormality of the liver
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0000969, Edema
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0000939, Osteoporosis
- HP:0001396, Cholestasis - HP:0001392, Abnormality of the liver
- HP:0001410, Decreased liver function - HP:0001392, Abnormality of the liver
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001392, Abnormality of the liver
- HP:0000938, Osteopenia - HP:0000939, Osteoporosis
- HP:0001642, Pulmonic stenosis - HP:0001712, Left ventricular hypertrophy
- HP:0200114, Metabolic alkalosis - HP:0002151, Increased serum lactate
- HP:0003073, Hypoalbuminemia - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0002151, Increased serum lactate
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology - HP:0009830, Peripheral neuropathy
- HP:0006568, Increased hepatic glycogen content - HP:0000819, Diabetes mellitus
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.501 in interactome to SLC25A4 and phenotypic similarity 0.472 to mouse mutant of SLC25A4.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0001625, cardiac hypertrophy
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0001625, cardiac hypertrophy
- HP:0200114, Metabolic alkalosis - MP:0030673, increased circulating alanine level
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0013405, increased circulating lactate level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.482 + (p=1.0E-1) +
+
+
+ Phenotype Score: 0.501 +
+
+
+ Variant Score: 0.872 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 4-127768852-C-T [0/1]
+
+
+ rs372171427
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.872
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SLC25A31:ENST00000281154.6:c.734C>T:p.(Thr245Ile) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8798723 + +
- REVEL: 0.785 +
- MVP: 0.880 +
+
+
+ -
+
- Frequency Data: + +
- TOPMed: 0.0113% +
- ESP AA: 0.0454% +
- ESP All: 0.0154% +
- ExAC AFR: 0.0481% +
- ExAC AMR: 0.0087% +
- ExAC EAS: 0.0116% +
- gnomAD_E_AFR: 0.0470% +
- gnomAD_E_AMR: 0.0032% +
- gnomAD_E_EAS: 0.0181% +
- gnomAD_G_AFR: 0.0573% +
- gnomAD_G_EAS: 0.0619% +
+
+
+
+
+
+
+
+ + + DNAJB5 + +
+
+
+ Exomiser Score: 0.474 + (p=1.1E-1) +
+
+
+ Phenotype Score: 0.503
+
+
+ Variant Score: 0.867
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.197 to zebrafish mutant involving DNAJB5.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0018468, axon peripheral neuron morphology, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.503 in interactome to CLPB and phenotypic similarity 0.640 to 3-methylglutaconic aciduria type 7 associated with CLPB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001397, Hepatic steatosis
- HP:0001903, Anemia - HP:0005528, Bone marrow hypocellularity
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0001875, Neutropenia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0005528, Bone marrow hypocellularity
- HP:0001396, Cholestasis - HP:0001397, Hepatic steatosis
- HP:0001410, Decreased liver function - HP:0000821, Hypothyroidism
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0000821, Hypothyroidism
- HP:0000938, Osteopenia - HP:0005528, Bone marrow hypocellularity
- HP:0001642, Pulmonic stenosis - HP:0001638, Cardiomyopathy
- HP:0200114, Metabolic alkalosis - HP:0002151, Increased serum lactate
- HP:0003073, Hypoalbuminemia - HP:0002151, Increased serum lactate
- HP:0003233, Decreased HDL cholesterol concentration - HP:0001397, Hepatic steatosis
- HP:0001873, Thrombocytopenia - HP:0001875, Neutropenia
- HP:0002151, Increased serum lactate - HP:0002151, Increased serum lactate
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001397, Hepatic steatosis
- HP:0004333, Bone-marrow foam cells - HP:0001875, Neutropenia
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.503 in interactome to CLPB and phenotypic similarity 0.212 to fish mutant of CLPB.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0012655, axon cerebellum morphology, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.474 + (p=1.1E-1) +
+
+
+ Phenotype Score: 0.503 +
+
+
+ Variant Score: 0.867 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 9-34996780-G-A [0/1]
+
+
+ rs562575065
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.867
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + DNAJB5:ENST00000682809.1:c.943G>A:p.(Val315Ile) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.87513155 + +
- REVEL: 0.399 +
- MVP: 0.875 +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0625% +
- TOPMed: 0.0068% +
- ExAC EAS: 0.0699% +
- ExAC SAS: 0.0305% +
- gnomAD_E_EAS: 0.0581% +
- gnomAD_E_NFE: 0.0018% +
- gnomAD_E_SAS: 0.0228% +
- gnomAD_G_EAS: 0.0617% +
+
+
+
+
+
+
+
+ + + ATAD3A + +
+
+
+ Exomiser Score: 0.462 + (p=1.1E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.864
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.553 to Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal associated with ATAD3A.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0002240, Hepatomegaly
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0002240, Hepatomegaly
- HP:0001410, Decreased liver function - HP:0002240, Hepatomegaly
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0002240, Hepatomegaly
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001639, Hypertrophic cardiomyopathy
- HP:0200114, Metabolic alkalosis - HP:0002151, Increased serum lactate
- HP:0003073, Hypoalbuminemia - HP:0002151, Increased serum lactate
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003146, Hypocholesterolemia
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0002151, Increased serum lactate
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0003477, Peripheral axonal neuropathy
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.458 to mouse mutant involving ATAD3A.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0000186, decreased circulating HDL cholesterol level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000186, decreased circulating HDL cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to USB1 and phenotypic similarity 0.640 to Dyskeratosis congenita associated with USB1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001903, Anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0005528, Bone marrow hypocellularity
- HP:0001396, Cholestasis - HP:0001399, Hepatic failure
- HP:0001410, Decreased liver function - HP:0001399, Hepatic failure
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001399, Hepatic failure
- HP:0000938, Osteopenia - HP:0000939, Osteoporosis
- HP:0001642, Pulmonic stenosis - HP:0100585, Telangiectasia of the skin
- HP:0200114, Metabolic alkalosis - HP:0000819, Diabetes mellitus
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0000819, Diabetes mellitus
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001394, Cirrhosis
- HP:0004333, Bone-marrow foam cells - HP:0001874, Abnormality of neutrophils
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to USB1 and phenotypic similarity 0.279 to mouse mutant of USB1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - MP:0001785, edema
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to USB1 and phenotypic similarity 0.208 to fish mutant of USB1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0001452, trunk edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.46 (p-value: 0.988820)
-
+
- Known diseases: +
- OMIM:617183 Harel-Yoon syndrome - autosomal dominant/recessive +
- OMIM:618810 Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal - autosomal recessive +
- ORPHA:496790 Ocular anomalies-axonal neuropathy-developmental delay syndrome - autosomal dominant/recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.462 + (p=1.1E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.864 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.485 to ORPHA:496790 Ocular anomalies-axonal neuropathy-developmental delay syndrome + +
- Phenotypic similarity 0.465 to OMIM:617183 Harel-Yoon syndrome + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 1-1524324-G-A [0/1]
+
+
+ rs1338018303
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PP3_Moderate]
+
+
+
+
+ Variant score: 0.864
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ATAD3A:ENST00000378756.8:c.1141G>A:p.(Val381Met) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8663908 + +
- REVEL: 0.809 +
- MVP: 0.866 +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_NFE: 0.0018% +
- gnomAD_E_OTH: 0.0183% +
+
+
+
+
+
+
+
+ + + ATXN1 + +
+
+
+ Exomiser Score: 0.447 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.507
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.288 to Spinocerebellar ataxia 1 associated with ATXN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0007006, Dorsal column degeneration
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.392 to mouse mutant involving ATXN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - MP:0004191, neuronal intranuclear inclusions
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0008489, slow postnatal weight gain
- Proximity score 0.507 in interactome to ATXN2 and phenotypic similarity 0.464 to Amyotrophic lateral sclerosis associated with ATXN2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0000217, Xerostomia
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function - HP:0000217, Xerostomia
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0000217, Xerostomia
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0000217, Xerostomia
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0000217, Xerostomia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0007373, Motor neuron atrophy
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.507 in interactome to ATXN2 and phenotypic similarity 0.675 to mouse mutant of ATXN2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002628, hepatic steatosis
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0002628, hepatic steatosis
- HP:0001410, Decreased liver function - MP:0002628, hepatic steatosis
- HP:0002910, Elevated hepatic transaminase - MP:0002628, hepatic steatosis
- HP:0001399, Hepatic failure - MP:0002628, hepatic steatosis
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0002079, increased circulating insulin level
- HP:0003073, Hypoalbuminemia - MP:0002079, increased circulating insulin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005178, increased circulating cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0002079, increased circulating insulin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002628, hepatic steatosis
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0010400, increased liver glycogen level
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0005455, increased susceptibility to weight gain
- PhenIX semantic similarity score: 0.38 (p-value: 0.844500)
-
+
- Known diseases: +
- OMIM:164400 Spinocerebellar ataxia 1 - autosomal dominant +
- ORPHA:98755 Spinocerebellar ataxia type 1 - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.447 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.507 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.288 to OMIM:164400 Spinocerebellar ataxia 1 + +
- Phenotypic similarity 0.204 to ORPHA:98755 Spinocerebellar ataxia type 1 + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 6-16327684-ATGC-A [-/1]
+
+
+ rs193922926
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ATXN1:ENST00000436367.6:c.624_626del:p.(Gln208del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.055 + (p=3.4E-1) +
+
+
+ Phenotype Score: 0.253 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_INSERTION
+ INS
+ 6-16327684-A-ATGCTGC [-/1]
+
+
+ rs193922926
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+ PATHOGENIC
+
+ (no assertion criteria provided)
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ATXN1:ENST00000436367.6:c.621_626dup:p.(Gln207_Gln208dup) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 6-16327684-ATGC-A [-/1]
+
+
+ rs193922926
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + ATXN1:ENST00000436367.6:c.624_626del:p.(Gln208del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + MUC12 + +
+
+
+ Exomiser Score: 0.445 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.506
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Proximity score 0.506 in interactome to GALNT1 and phenotypic similarity 0.745 to mouse mutant of GALNT1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0008482, decreased spleen germinal center number
- HP:0001903, Anemia - MP:0002607, decreased basophil cell number
- HP:0001541, Ascites - MP:0005606, increased bleeding time
- HP:0010972, Anemia of inadequate production - MP:0005012, decreased eosinophil cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0002607, decreased basophil cell number
- HP:0001396, Cholestasis - MP:0008482, decreased spleen germinal center number
- HP:0001410, Decreased liver function - MP:0008482, decreased spleen germinal center number
- HP:0002910, Elevated hepatic transaminase - MP:0008482, decreased spleen germinal center number
- HP:0001399, Hepatic failure - MP:0008482, decreased spleen germinal center number
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0006128, pulmonary valve stenosis
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - MP:0005419, decreased circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005419, decreased circulating serum albumin level
- HP:0001873, Thrombocytopenia - MP:0002607, decreased basophil cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0008482, decreased spleen germinal center number
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0008482, decreased spleen germinal center number
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0008482, decreased spleen germinal center number
- HP:0004333, Bone-marrow foam cells - MP:0010470, dilated ascending aorta
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.445 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.506 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ INFRAME_INSERTION
+ INS
+ 7-100969674-A-ACTG [0/1]
+
+
+ rs150485202
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, PM4]
+
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + MUC12:ENST00000536621.6:c.54_55insGCT:p.(Thr18_Thr19insAla) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.389 + (p=1.4E-1) +
+
+
+ Phenotype Score: 0.506 +
+
+
+ Variant Score: 0.825 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ INFRAME_INSERTION
+ INS
+ 7-100969674-A-ACTG [0/1]
+
+
+ rs150485202
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, PM4]
+
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + MUC12:ENST00000536621.6:c.54_55insGCT:p.(Thr18_Thr19insAla) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+ SPLICE_REGION_VARIANT
+ SNV
+ 7-100969688-A-G [0/1]
+
+
+ rs73168328
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.800
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + MUC12:ENST00000536621.6:c.66A>G:p.(=) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+ Other passed variants:
+
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 7-100969671-G-A [0/1]
+
+
+ rs79881008
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ Variant score: 0.012
+
+
+ -
+
- Transcripts: +
- + + MUC12:ENST00000536621.6:c.49G>A:p.(Val17Ile) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.012 + +
- REVEL: 0.012 +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + CEL + +
+
+
+ Exomiser Score: 0.437 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.517
+
+
+ Variant Score: 0.834
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.476 to MODY associated with CEL.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0012028, Hepatocellular adenoma
- HP:0001903, Anemia - HP:0040217, Elevated hemoglobin A1c
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0040217, Elevated hemoglobin A1c
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0040217, Elevated hemoglobin A1c
- HP:0001396, Cholestasis - HP:0012028, Hepatocellular adenoma
- HP:0001410, Decreased liver function - HP:0001738, Exocrine pancreatic insufficiency
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001738, Exocrine pancreatic insufficiency
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0000825, Hyperinsulinemic hypoglycemia
- HP:0003073, Hypoalbuminemia - HP:0030794, Abnormal circulating C-peptide concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0030794, Abnormal circulating C-peptide concentration
- HP:0001873, Thrombocytopenia - HP:0040217, Elevated hemoglobin A1c
- HP:0002151, Increased serum lactate - HP:0000825, Hyperinsulinemic hypoglycemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0000831, Insulin-resistant diabetes mellitus
- HP:0004333, Bone-marrow foam cells - HP:0040217, Elevated hemoglobin A1c
- HP:0001531, Failure to thrive in infancy - HP:0001520, Large for gestational age
- Phenotypic similarity 0.236 to mouse mutant involving CEL.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0005342, abnormal intestinal lipid absorption
- HP:0001410, Decreased liver function - MP:0005342, abnormal intestinal lipid absorption
- HP:0002910, Elevated hepatic transaminase - MP:0005342, abnormal intestinal lipid absorption
- HP:0001399, Hepatic failure - MP:0005342, abnormal intestinal lipid absorption
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005342, abnormal intestinal lipid absorption
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0005342, abnormal intestinal lipid absorption
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0005342, abnormal intestinal lipid absorption
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.517 in interactome to LIPA and phenotypic similarity 0.854 to Cholesteryl ester storage disease associated with LIPA.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001433, Hepatosplenomegaly
- HP:0001903, Anemia - HP:0001903, Anemia
- HP:0001541, Ascites - HP:0001538, Protuberant abdomen
- HP:0010972, Anemia of inadequate production - HP:0001903, Anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001882, Leukopenia
- HP:0001396, Cholestasis - HP:0001399, Hepatic failure
- HP:0001410, Decreased liver function - HP:0001399, Hepatic failure
- HP:0002910, Elevated hepatic transaminase - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0001399, Hepatic failure - HP:0001399, Hepatic failure
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001409, Portal hypertension
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - HP:0003282, Low alkaline phosphatase
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003233, Decreased HDL cholesterol concentration
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0002155, Hypertriglyceridemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0031956, Elevated circulating aspartate aminotransferase concentration
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001397, Hepatic steatosis
- HP:0004333, Bone-marrow foam cells - HP:0004333, Bone-marrow foam cells
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.517 in interactome to LIPA and phenotypic similarity 0.706 to mouse mutant of LIPA.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0031058, hepatosplenomegaly
- HP:0001903, Anemia - MP:0008245, abnormal alveolar macrophage morphology
- HP:0001541, Ascites - MP:0002981, increased liver weight
- HP:0010972, Anemia of inadequate production - MP:0008245, abnormal alveolar macrophage morphology
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0008245, abnormal alveolar macrophage morphology
- HP:0001396, Cholestasis - MP:0000598, abnormal liver morphology
- HP:0001410, Decreased liver function - MP:0000598, abnormal liver morphology
- HP:0002910, Elevated hepatic transaminase - MP:0000598, abnormal liver morphology
- HP:0001399, Hepatic failure - MP:0000598, abnormal liver morphology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0002079, increased circulating insulin level
- HP:0003073, Hypoalbuminemia - MP:0002079, increased circulating insulin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000186, decreased circulating HDL cholesterol level
- HP:0001873, Thrombocytopenia - MP:0008245, abnormal alveolar macrophage morphology
- HP:0002151, Increased serum lactate - MP:0001554, increased circulating free fatty acids level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000598, abnormal liver morphology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000598, abnormal liver morphology
- HP:0002366, Abnormal lower motor neuron morphology - MP:0000820, abnormal choroid plexus morphology
- HP:0006568, Increased hepatic glycogen content - MP:0002628, hepatic steatosis
- HP:0004333, Bone-marrow foam cells - MP:0008245, abnormal alveolar macrophage morphology
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- PhenIX semantic similarity score: 0.63 (p-value: 0.000390)
-
+
- Known diseases: +
- OMIM:609812 Maturity-onset diabetes of the young, type VIII - autosomal dominant +
- ORPHA:552 MODY - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.437 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.517 +
+
+
+ Variant Score: 0.834 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.476 to ORPHA:552 MODY + +
- Phenotypic similarity 0.434 to OMIM:609812 Maturity-onset diabetes of the young, type VIII + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 9-133068761-G-A [0/1]
+
+
+ rs746397927
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+ LIKELY_BENIGN
+
+
+
+
+ [BP4]
+
+
+
+
+ Variant score: 0.834
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + CEL:ENST00000372080.8:c.985G>A:p.(Asp329Asn) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.841606 + +
- REVEL: 0.269 +
- MVP: 0.842 +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_AFR: 0.0167% +
- gnomAD_E_EAS: 0.0324% +
- gnomAD_E_NFE: 0.0020% +
- gnomAD_E_OTH: 0.0200% +
- gnomAD_E_SAS: 0.0071% +
- gnomAD_G_AFR: 0.0247% +
- gnomAD_G_EAS: 0.0632% +
+
+
+
+
+
+
+
+ + + MADCAM1 + +
+
+
+ Exomiser Score: 0.433 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.501
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.277 to mouse mutant involving MADCAM1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0008135, small Peyer's patches
- HP:0001903, Anemia - MP:0005017, decreased B cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0005017, decreased B cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0005017, decreased B cell number
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0005017, decreased B cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0005017, decreased B cell number
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to IL10 and phenotypic similarity 0.493 to Systemic lupus erythematosus associated with IL10.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0002716, Lymphadenopathy
- HP:0001903, Anemia - HP:0001878, Hemolytic anemia
- HP:0001541, Ascites - HP:0100755, Abnormality of salivation
- HP:0010972, Anemia of inadequate production - HP:0001878, Hemolytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001882, Leukopenia
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - HP:0001369, Arthritis
- HP:0001642, Pulmonic stenosis - HP:0000822, Hypertension
- HP:0200114, Metabolic alkalosis - HP:0100755, Abnormality of salivation
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0001873, Thrombocytopenia
- HP:0002151, Increased serum lactate - HP:0100755, Abnormality of salivation
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - HP:0001882, Leukopenia
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to IL10 and phenotypic similarity 0.742 to mouse mutant of IL10.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0008477, decreased spleen red pulp amount
- HP:0001903, Anemia - MP:0001577, anemia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0002810, microcytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0008246, abnormal leukocyte morphology
- HP:0001396, Cholestasis - MP:0000609, abnormal liver physiology
- HP:0001410, Decreased liver function - MP:0000609, abnormal liver physiology
- HP:0002910, Elevated hepatic transaminase - MP:0000609, abnormal liver physiology
- HP:0001399, Hepatic failure - MP:0000609, abnormal liver physiology
- HP:0000938, Osteopenia - MP:0002896, abnormal bone mineralization
- HP:0001642, Pulmonic stenosis - MP:0003037, increased myocardial infarct size
- HP:0200114, Metabolic alkalosis - MP:0005554, decreased circulating creatinine level
- HP:0003073, Hypoalbuminemia - MP:0000199, abnormal circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0005179, decreased circulating cholesterol level
- HP:0001873, Thrombocytopenia - MP:0002875, decreased erythrocyte cell number
- HP:0002151, Increased serum lactate - MP:0005554, decreased circulating creatinine level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000609, abnormal liver physiology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000609, abnormal liver physiology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0009355, increased liver triglyceride level
- HP:0004333, Bone-marrow foam cells - MP:0000322, increased granulocyte number
- HP:0001531, Failure to thrive in infancy - MP:0001732, postnatal growth retardation
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.433 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.501 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_INSERTION
+ INS
+ 19-501743-T-TCTCCCGACACCACCTCCCCGGAGTCTCCCGACACCACCTCCCAGGAGC [-/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+
+
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + KCNN3 + +
+
+
+ Exomiser Score: 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.394 to Zimmermann-Laband syndrome associated with KCNN3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001744, Splenomegaly
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001744, Splenomegaly
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001744, Splenomegaly
- HP:0001396, Cholestasis - HP:0002240, Hepatomegaly
- HP:0001410, Decreased liver function - HP:0002240, Hepatomegaly
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0002240, Hepatomegaly
- HP:0000938, Osteopenia - HP:0001382, Joint hypermobility
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0001744, Splenomegaly
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells - HP:0001744, Splenomegaly
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to BPNT1 and phenotypic similarity 0.638 to mouse mutant of BPNT1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000599, enlarged liver
- HP:0001903, Anemia -
- HP:0001541, Ascites - MP:0011738, anasarca
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0000603, pale liver
- HP:0001410, Decreased liver function - MP:0000603, pale liver
- HP:0002910, Elevated hepatic transaminase - MP:0000603, pale liver
- HP:0001399, Hepatic failure - MP:0000603, pale liver
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005343, increased circulating aspartate transaminase level
- HP:0003073, Hypoalbuminemia - MP:0005419, decreased circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0003983, decreased cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0005343, increased circulating aspartate transaminase level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000603, pale liver
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000603, pale liver
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000607, abnormal hepatocyte morphology
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
-
+
- Known diseases: +
- OMIM:618658 Zimmermann-Laband syndrome 3 - autosomal dominant +
- ORPHA:3473 Zimmermann-Laband syndrome - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.394 to ORPHA:3473 Zimmermann-Laband syndrome + +
- Phenotypic similarity 0.179 to OMIM:618658 Zimmermann-Laband syndrome 3 + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 1-154869723-GGCTGCTGCT-G [-/1]
+
+
+ rs3831942
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, BP6]
+
+
+
+ ClinVar:
+
+ BENIGN
+
+
+
+
+
+
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + KCNN3:ENST00000271915.9:c.233_241del:p.(Gln78_Gln80del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + SCRT2 + +
+
+
+ Exomiser Score: 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.254 to zebrafish mutant involving SCRT2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0003800, spinal cord has extra parts of type neuron, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to IRF2BP2 and phenotypic similarity 0.667 to Common variable immunodeficiency associated with IRF2BP2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001878, Hemolytic anemia
- HP:0001541, Ascites - HP:0001744, Splenomegaly
- HP:0010972, Anemia of inadequate production - HP:0001878, Hemolytic anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001888, Lymphopenia
- HP:0001396, Cholestasis - HP:0001392, Abnormality of the liver
- HP:0001410, Decreased liver function - HP:0001392, Abnormality of the liver
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0001392, Abnormality of the liver
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0000979, Purpura
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - HP:0001973, Autoimmune thrombocytopenia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001392, Abnormality of the liver
- HP:0004333, Bone-marrow foam cells - HP:0001888, Lymphopenia
- HP:0001531, Failure to thrive in infancy - HP:0001531, Failure to thrive in infancy
- Proximity score 0.500 in interactome to IRF2BP2 and phenotypic similarity 0.543 to mouse mutant of IRF2BP2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000598, abnormal liver morphology
- HP:0001903, Anemia - MP:0002875, decreased erythrocyte cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0004229, abnormal embryonic erythropoiesis
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0002416, abnormal proerythroblast morphology
- HP:0001396, Cholestasis - MP:0000598, abnormal liver morphology
- HP:0001410, Decreased liver function - MP:0000598, abnormal liver morphology
- HP:0002910, Elevated hepatic transaminase - MP:0000598, abnormal liver morphology
- HP:0001399, Hepatic failure - MP:0000598, abnormal liver morphology
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0002875, decreased erythrocyte cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000598, abnormal liver morphology
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000598, abnormal liver morphology
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000598, abnormal liver morphology
- HP:0004333, Bone-marrow foam cells - MP:0002416, abnormal proerythroblast morphology
- HP:0001531, Failure to thrive in infancy - MP:0001732, postnatal growth retardation
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ INFRAME_INSERTION
+ INS
+ 20-663718-T-TGGCGCAGGCCGCCTC [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting, PM4]
+
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + SCRT2:ENST00000246104.7:c.862_876dup:p.(Glu288_Ala292dup) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + UTF1 + +
+
+
+ Exomiser Score: 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.326 to mouse mutant involving UTF1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0000060, delayed bone ossification
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - MP:0000060, delayed bone ossification
- HP:0001642, Pulmonic stenosis - MP:0002652, thin myocardium
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0004201, fetal growth retardation
- Proximity score 0.500 in interactome to ZSCAN10 and phenotypic similarity 0.676 to mouse mutant of ZSCAN10.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002981, increased liver weight
- HP:0001903, Anemia - MP:0002599, increased mean platelet volume
- HP:0001541, Ascites - MP:0002981, increased liver weight
- HP:0010972, Anemia of inadequate production - MP:0005014, increased B cell number
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0004016, decreased bone mass
- HP:0001396, Cholestasis - MP:0002981, increased liver weight
- HP:0001410, Decreased liver function - MP:0002981, increased liver weight
- HP:0002910, Elevated hepatic transaminase - MP:0002981, increased liver weight
- HP:0001399, Hepatic failure - MP:0002981, increased liver weight
- HP:0000938, Osteopenia - MP:0004016, decreased bone mass
- HP:0001642, Pulmonic stenosis - MP:0003921, abnormal heart left ventricle morphology
- HP:0200114, Metabolic alkalosis - MP:0003020, decreased circulating chloride level
- HP:0003073, Hypoalbuminemia - MP:0005419, decreased circulating serum albumin level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0002665, decreased circulating corticosterone level
- HP:0001873, Thrombocytopenia - MP:0003179, thrombocytopenia
- HP:0002151, Increased serum lactate - MP:0005553, increased circulating creatinine level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0002981, increased liver weight
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0002981, increased liver weight
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0002981, increased liver weight
- HP:0004333, Bone-marrow foam cells - MP:0003944, abnormal T cell subpopulation ratio
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 10-133230985-CCGCCCG-C [0/1]
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + UTF1:ENST00000304477.3:c.572_577del:p.(Ala191_Arg192del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + LNP1 + +
+
+
+ Exomiser Score: 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.850
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Proximity score 0.500 in interactome to SCO1 and phenotypic similarity 0.675 to Mitochondrial complex IV deficiency, nuclear type 4 associated with SCO1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0002240, Hepatomegaly
- HP:0001903, Anemia -
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - HP:0002240, Hepatomegaly
- HP:0001410, Decreased liver function - HP:0002240, Hepatomegaly
- HP:0002910, Elevated hepatic transaminase - HP:0031956, Elevated circulating aspartate aminotransferase concentration
- HP:0001399, Hepatic failure - HP:0002240, Hepatomegaly
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001714, Ventricular hypertrophy
- HP:0200114, Metabolic alkalosis - HP:0001942, Metabolic acidosis
- HP:0003073, Hypoalbuminemia - HP:0002151, Increased serum lactate
- HP:0003233, Decreased HDL cholesterol concentration - HP:0008315, Decreased plasma free carnitine
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - HP:0002151, Increased serum lactate
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0031956, Elevated circulating aspartate aminotransferase concentration
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001397, Hepatic steatosis
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.430 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.850 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_INSERTION
+ INS
+ 3-100451756-A-ATCCTAGAAGGCATTCTCATGAGGACCAGGAATTCCGATGCCGATCGTCTGACCGTCT [1/1]
+
+
+ rs71132521
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ [PM2_Supporting]
+
+
+
+
+ Variant score: 0.850
+ CONTRIBUTING VARIANT
+
+
+
+
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: +
- No frequency data + +
+
+
+
+
+
+
+
+ + + CORO6 + +
+
+
+ Exomiser Score: 0.429 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.502
+
+
+ Variant Score: 0.848
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Proximity score 0.502 in interactome to MYO5B and phenotypic similarity 0.716 to Cholestasis, progressive familial intrahepatic, 10 associated with MYO5B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0001744, Splenomegaly
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0001744, Splenomegaly
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001744, Splenomegaly
- HP:0001396, Cholestasis - HP:0011985, Acholic stools
- HP:0001410, Decreased liver function - HP:0011985, Acholic stools
- HP:0002910, Elevated hepatic transaminase - HP:0031956, Elevated circulating aspartate aminotransferase concentration
- HP:0001399, Hepatic failure - HP:0011985, Acholic stools
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - HP:0003573, Increased total bilirubin
- HP:0003073, Hypoalbuminemia - HP:0003073, Hypoalbuminemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003124, Hypercholesterolemia
- HP:0001873, Thrombocytopenia - HP:0001744, Splenomegaly
- HP:0002151, Increased serum lactate - HP:0003573, Increased total bilirubin
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0031964, Elevated circulating alanine aminotransferase concentration
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0031956, Elevated circulating aspartate aminotransferase concentration
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0002240, Hepatomegaly
- HP:0004333, Bone-marrow foam cells - HP:0001744, Splenomegaly
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.502 in interactome to MYO5B and phenotypic similarity 0.330 to mouse mutant of MYO5B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0005036, diarrhea
- HP:0001410, Decreased liver function - MP:0005036, diarrhea
- HP:0002910, Elevated hepatic transaminase - MP:0005036, diarrhea
- HP:0001399, Hepatic failure - MP:0005036, diarrhea
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0005036, diarrhea
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0005036, diarrhea
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0000189, hypoglycemia
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.502 in interactome to MYO5B and phenotypic similarity 0.245 to fish mutant of MYO5B.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - ZP:0006598, cardiac ventricle hypotrophic, abnormal
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - ZP:0011709, cranial nerve II has fewer parts of type axon retinal ganglion cell, abnormal
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - ZP:0107218, cardiac ventricle decreased occurrence cardiac chamber ballooning, abnormal
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.429 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.502 +
+
+
+ Variant Score: 0.848 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ MISSENSE_VARIANT
+ SNV
+ 17-29616744-A-G [0/1]
+
+
+ rs377223092
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.848
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + CORO6:ENST00000388767.8:c.962T>C:p.(Met321Thr) + + +
+
+
+ -
+
- Pathogenicity Data: +
- Best Score: 0.8591861 + +
- REVEL: 0.639 +
- MVP: 0.859 +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0937% +
- TOPMed: 0.0937% +
- ExAC EAS: 0.0925% +
- gnomAD_E_EAS: 0.0812% +
- gnomAD_E_OTH: 0.0182% +
- gnomAD_E_SAS: 0.0097% +
- gnomAD_G_NFE: 0.0067% +
+
+
+
+
+
+
+
+ + + DSPP + +
+
+
+ Exomiser Score: 0.428 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.501
+
+
+ Variant Score: 0.848
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.247 to mouse mutant involving DSPP.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0030484, abnormal osteocyte lacuna morphology
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia - MP:0030484, abnormal osteocyte lacuna morphology
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.501 in interactome to HSPG2 and phenotypic similarity 0.507 to 1p36 deletion syndrome associated with HSPG2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001743, Abnormality of the spleen
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0000902, Rib fusion
- HP:0001396, Cholestasis - HP:0001392, Abnormality of the liver
- HP:0001410, Decreased liver function - HP:0001392, Abnormality of the liver
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001392, Abnormality of the liver
- HP:0000938, Osteopenia - HP:0000902, Rib fusion
- HP:0001642, Pulmonic stenosis - HP:0001636, Tetralogy of Fallot
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration - HP:0001397, Hepatic steatosis
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - HP:0003416, Spinal canal stenosis
- HP:0006568, Increased hepatic glycogen content - HP:0001397, Hepatic steatosis
- HP:0004333, Bone-marrow foam cells - HP:0005113, Aortic arch aneurysm
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.501 in interactome to HSPG2 and phenotypic similarity 0.609 to mouse mutant of HSPG2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0000602, dilated liver sinusoidal space
- HP:0001903, Anemia -
- HP:0001541, Ascites - MP:0005244, hemopericardium
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0000065, abnormal bone marrow cavity morphology
- HP:0001396, Cholestasis - MP:0000602, dilated liver sinusoidal space
- HP:0001410, Decreased liver function - MP:0000602, dilated liver sinusoidal space
- HP:0002910, Elevated hepatic transaminase - MP:0000602, dilated liver sinusoidal space
- HP:0001399, Hepatic failure - MP:0000602, dilated liver sinusoidal space
- HP:0000938, Osteopenia - MP:0008272, abnormal endochondral bone ossification
- HP:0001642, Pulmonic stenosis - MP:0002748, abnormal pulmonary valve morphology
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0000602, dilated liver sinusoidal space
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0000602, dilated liver sinusoidal space
- HP:0002366, Abnormal lower motor neuron morphology - MP:0002152, abnormal brain morphology
- HP:0006568, Increased hepatic glycogen content - MP:0000602, dilated liver sinusoidal space
- HP:0004333, Bone-marrow foam cells - MP:0010472, abnormal ascending aorta and coronary artery attachment
- HP:0001531, Failure to thrive in infancy - MP:0000547, short limbs
- Proximity score 0.501 in interactome to HSPG2 and phenotypic similarity 0.222 to fish mutant of HSPG2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites - ZP:0000038, pericardium edematous, abnormal
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - ZP:0006851, cardiac ventricle elongated, abnormal
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - ZP:0000530, dorsal aorta collapsed, abnormal
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.03 (p-value: 0.999050)
-
+
- Known diseases: +
- OMIM:125420 Dentin dysplasia, type II - autosomal dominant +
- OMIM:125490 Dentinogenesis imperfecta, Shields type II - autosomal dominant +
- OMIM:125500 Dentinogenesis imperfecta, Shields type III - autosomal dominant +
- OMIM:605594 Deafness, autosomal dominant 39, with dentinogenesis - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.428 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.501 +
+
+
+ Variant Score: 0.848 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 4-87615776-CAGCAGCGAT-C [0/1]
+
+
+ rs763791363
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.848
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + DSPP:ENST00000651931.1:c.3120_3128del:p.(Asp1053_Ser1055del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_AMR: 0.0048% +
- gnomAD_E_EAS: 0.0114% +
- gnomAD_E_NFE: 0.0062% +
- gnomAD_E_SAS: 0.0048% +
- gnomAD_G_NFE: 0.0173% +
+
+
+
+
+
+
+
+ + + EDC4 + +
+
+
+ Exomiser Score: 0.427 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.849
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+ No known disease
+
+ - Phenotypic similarity 0.355 to mouse mutant involving EDC4.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0002875, decreased erythrocyte cell number
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0002875, decreased erythrocyte cell number
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0002875, decreased erythrocyte cell number
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0002875, decreased erythrocyte cell number
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.500 in interactome to SKIC3 and phenotypic similarity 0.689 to Trichohepatoenteric syndrome 1 associated with SKIC3.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001744, Splenomegaly
- HP:0001903, Anemia - HP:0011877, Increased mean platelet volume
- HP:0001541, Ascites - HP:0002240, Hepatomegaly
- HP:0010972, Anemia of inadequate production - HP:0011877, Increased mean platelet volume
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0011877, Increased mean platelet volume
- HP:0001396, Cholestasis - HP:0001396, Cholestasis
- HP:0001410, Decreased liver function - HP:0001399, Hepatic failure
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0001399, Hepatic failure
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001642, Pulmonic stenosis
- HP:0200114, Metabolic alkalosis - HP:0003235, Hypermethioninemia
- HP:0003073, Hypoalbuminemia - HP:0003073, Hypoalbuminemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003073, Hypoalbuminemia
- HP:0001873, Thrombocytopenia - HP:0001894, Thrombocytosis
- HP:0002151, Increased serum lactate - HP:0003235, Hypermethioninemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001395, Hepatic fibrosis
- HP:0004333, Bone-marrow foam cells - HP:0011877, Increased mean platelet volume
- HP:0001531, Failure to thrive in infancy - HP:0001508, Failure to thrive
- Proximity score 0.500 in interactome to TTC37 and phenotypic similarity 0.361 to mouse mutant of TTC37.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0011874, enlarged urinary bladder
- HP:0001903, Anemia - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0005627, increased circulating potassium level
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0002151, Increased serum lactate - MP:0005627, increased circulating potassium level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0005641, increased mean corpuscular hemoglobin concentration
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.427 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.849 +
+
+
+
+
+
+
+ No phenotype matches to diseases with this MOI.
+
+
+
+
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 16-67879894-CAGCAGCAGT-C [0/1]
+
+
+ rs769592693
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.849
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + EDC4:ENST00000358933.10:c.1875_1883del:p.(Ser627_Ser629del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- ExAC NFE: 0.0031% +
- ExAC SAS: 0.0122% +
- gnomAD_E_AMR: 0.0030% +
- gnomAD_E_NFE: 0.0036% +
- gnomAD_E_SAS: 0.0097% +
- gnomAD_G_AFR: 0.0115% +
+
+
+
+
+
+
+
+ + + LMOD2 + +
+
+
+ Exomiser Score: 0.426 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500
+
+
+ Variant Score: 0.848
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.379 to Familial isolated dilated cardiomyopathy associated with LMOD2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001874, Abnormality of neutrophils
- HP:0001903, Anemia - HP:0001874, Abnormality of neutrophils
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0001874, Abnormality of neutrophils
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001874, Abnormality of neutrophils
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - HP:0001644, Dilated cardiomyopathy
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0003233, Decreased HDL cholesterol concentration - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0001873, Thrombocytopenia - HP:0001874, Abnormality of neutrophils
- HP:0002151, Increased serum lactate - HP:0003236, Elevated circulating creatine kinase concentration
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - HP:0001874, Abnormality of neutrophils
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.327 to mouse mutant involving LMOD2.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0002833, increased heart weight
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0000280, thin ventricular wall
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001262, decreased body weight
- Proximity score 0.500 in interactome to TCF4 and phenotypic similarity 0.727 to Primary sclerosing cholangitis associated with TCF4.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001433, Hepatosplenomegaly
- HP:0001903, Anemia - HP:0001879, Abnormal eosinophil morphology
- HP:0001541, Ascites - HP:0001541, Ascites
- HP:0010972, Anemia of inadequate production - HP:0001879, Abnormal eosinophil morphology
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001879, Abnormal eosinophil morphology
- HP:0001396, Cholestasis - HP:0001396, Cholestasis
- HP:0001410, Decreased liver function - HP:0100626, Chronic hepatic failure
- HP:0002910, Elevated hepatic transaminase - HP:0002910, Elevated hepatic transaminase
- HP:0001399, Hepatic failure - HP:0100626, Chronic hepatic failure
- HP:0000938, Osteopenia - HP:0000938, Osteopenia
- HP:0001642, Pulmonic stenosis - HP:0001635, Congestive heart failure
- HP:0200114, Metabolic alkalosis - HP:0001945, Fever
- HP:0003073, Hypoalbuminemia - HP:0003073, Hypoalbuminemia
- HP:0003233, Decreased HDL cholesterol concentration - HP:0100512, Low levels of vitamin D
- HP:0001873, Thrombocytopenia - HP:0001879, Abnormal eosinophil morphology
- HP:0002151, Increased serum lactate - HP:0003073, Hypoalbuminemia
- HP:0031964, Elevated circulating alanine aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - HP:0002910, Elevated hepatic transaminase
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0001394, Cirrhosis
- HP:0004333, Bone-marrow foam cells - HP:0100727, Histiocytosis
- HP:0001531, Failure to thrive in infancy - HP:0001824, Weight loss
- Proximity score 0.500 in interactome to TCF4 and phenotypic similarity 0.315 to mouse mutant of TCF4.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0005090, increased double-negative T cell number
- HP:0001903, Anemia - MP:0002145, abnormal T cell differentiation
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0002145, abnormal T cell differentiation
- HP:0005561, Abnormality of bone marrow cell morphology - MP:0002145, abnormal T cell differentiation
- HP:0001396, Cholestasis - MP:0005090, increased double-negative T cell number
- HP:0001410, Decreased liver function - MP:0005090, increased double-negative T cell number
- HP:0002910, Elevated hepatic transaminase - MP:0005090, increased double-negative T cell number
- HP:0001399, Hepatic failure - MP:0005090, increased double-negative T cell number
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0002145, abnormal T cell differentiation
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0005090, increased double-negative T cell number
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0005090, increased double-negative T cell number
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0005090, increased double-negative T cell number
- HP:0004333, Bone-marrow foam cells - MP:0002145, abnormal T cell differentiation
- HP:0001531, Failure to thrive in infancy -
- PhenIX semantic similarity score: 0.00 (p-value: 1.000000)
-
+
- Known diseases: +
- OMIM:619897 Cardiomyopathy, dilated, 2G - autosomal recessive +
- ORPHA:154 Familial isolated dilated cardiomyopathy - autosomal recessive +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_RECESSIVE
+
+
+ Exomiser Score: + 0.426 + (p=1.2E-1) +
+
+
+ Phenotype Score: 0.500 +
+
+
+ Variant Score: 0.848 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.379 to ORPHA:154 Familial isolated dilated cardiomyopathy + +
- Phenotypic similarity 0.259 to OMIM:619897 Cardiomyopathy, dilated, 2G + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ DISRUPTIVE_INFRAME_DELETION
+ DEL
+ 7-123662846-ACCT-A [1/1]
+
+
+ rs577158076
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+
+ Variant score: 0.848
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + LMOD2:ENST00000458573.3:c.1272_1274del:p.(Pro433del) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- gnomAD_E_AFR: 0.0147% +
- gnomAD_E_AMR: 0.0032% +
- gnomAD_E_FIN: 0.0048% +
- gnomAD_E_NFE: 0.0020% +
+
+
+
+
+
+
+
+
+
+
+ + + FN1 + +
+
+
+ Exomiser Score: 0.409 + (p=1.3E-1) +
+
+
+ Phenotype Score: 0.538
+
+
+ Variant Score: 0.797
+
+
+
+
+
+ Phenotype matches:
+
+
+
+
+
+
+ - Phenotypic similarity 0.538 to Spondylometaphyseal dysplasia, 'corner fracture' type associated with FN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - HP:0001891, Iron deficiency anemia
- HP:0001903, Anemia - HP:0001891, Iron deficiency anemia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - HP:0001891, Iron deficiency anemia
- HP:0005561, Abnormality of bone marrow cell morphology - HP:0001891, Iron deficiency anemia
- HP:0001396, Cholestasis - HP:0031427, Abnormal circulating osteocalcin level
- HP:0001410, Decreased liver function - HP:0031427, Abnormal circulating osteocalcin level
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure - HP:0031427, Abnormal circulating osteocalcin level
- HP:0000938, Osteopenia - HP:0004349, Reduced bone mineral density
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia - HP:0031427, Abnormal circulating osteocalcin level
- HP:0003233, Decreased HDL cholesterol concentration - HP:0031427, Abnormal circulating osteocalcin level
- HP:0001873, Thrombocytopenia - HP:0001891, Iron deficiency anemia
- HP:0002151, Increased serum lactate - HP:0031427, Abnormal circulating osteocalcin level
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - HP:0031427, Abnormal circulating osteocalcin level
- HP:0004333, Bone-marrow foam cells - HP:0001891, Iron deficiency anemia
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.437 to mouse mutant involving FN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia - MP:0001577, anemia
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production - MP:0001577, anemia
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - MP:0000292, distended pericardium
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia - MP:0001577, anemia
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology - MP:0003400, kinked neural tube
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells - MP:0001577, anemia
- HP:0001531, Failure to thrive in infancy -
- Phenotypic similarity 0.222 to zebrafish mutant involving FN1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly -
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis -
- HP:0001410, Decreased liver function -
- HP:0002910, Elevated hepatic transaminase -
- HP:0001399, Hepatic failure -
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis - ZP:0001722, atrioventricular valve morphology, abnormal
- HP:0200114, Metabolic alkalosis -
- HP:0003073, Hypoalbuminemia -
- HP:0003233, Decreased HDL cholesterol concentration -
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate -
- HP:0031964, Elevated circulating alanine aminotransferase concentration -
- HP:0031956, Elevated circulating aspartate aminotransferase concentration -
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content -
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy -
- Proximity score 0.519 in interactome to FGL1 and phenotypic similarity 0.605 to mouse mutant of FGL1.
- Best Phenotype Matches:
- HP:0000007, Autosomal recessive inheritance -
- HP:0001433, Hepatosplenomegaly - MP:0004847, abnormal liver weight
- HP:0001903, Anemia -
- HP:0001541, Ascites -
- HP:0010972, Anemia of inadequate production -
- HP:0005561, Abnormality of bone marrow cell morphology -
- HP:0001396, Cholestasis - MP:0004847, abnormal liver weight
- HP:0001410, Decreased liver function - MP:0004847, abnormal liver weight
- HP:0002910, Elevated hepatic transaminase - MP:0004847, abnormal liver weight
- HP:0001399, Hepatic failure - MP:0004847, abnormal liver weight
- HP:0000938, Osteopenia -
- HP:0001642, Pulmonic stenosis -
- HP:0200114, Metabolic alkalosis - MP:0002702, decreased circulating free fatty acids level
- HP:0003073, Hypoalbuminemia - MP:0000186, decreased circulating HDL cholesterol level
- HP:0003233, Decreased HDL cholesterol concentration - MP:0000186, decreased circulating HDL cholesterol level
- HP:0001873, Thrombocytopenia -
- HP:0002151, Increased serum lactate - MP:0002702, decreased circulating free fatty acids level
- HP:0031964, Elevated circulating alanine aminotransferase concentration - MP:0004847, abnormal liver weight
- HP:0031956, Elevated circulating aspartate aminotransferase concentration - MP:0004847, abnormal liver weight
- HP:0002366, Abnormal lower motor neuron morphology -
- HP:0006568, Increased hepatic glycogen content - MP:0031115, macrovesicular hepatic steatosis
- HP:0004333, Bone-marrow foam cells -
- HP:0001531, Failure to thrive in infancy - MP:0001260, increased body weight
- PhenIX semantic similarity score: 0.90 (p-value: 0.714220)
-
+
- Known diseases: +
- OMIM:184255 Spondylometaphyseal dysplasia, corner fracture type - autosomal dominant +
- OMIM:601894 Glomerulopathy with fibronectin deposits 2 - autosomal dominant +
- ORPHA:84090 Fibronectin glomerulopathy - autosomal dominant +
- ORPHA:93315 Spondylometaphyseal dysplasia, 'corner fracture' type - autosomal dominant +
+
+
+
+ Gene scores under compatible inheritance modes:
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ AUTOSOMAL_DOMINANT
+
+
+ Exomiser Score: + 0.409 + (p=1.3E-1) +
+
+
+ Phenotype Score: 0.538 +
+
+
+ Variant Score: 0.797 +
+
+
+
+
+
+
+
+ -
+
+
- + Phenotype matches to diseases consistent with this MOI: + + + + + + +
- Phenotypic similarity 0.538 to ORPHA:93315 Spondylometaphyseal dysplasia, 'corner fracture' type + +
- Phenotypic similarity 0.507 to ORPHA:84090 Fibronectin glomerulopathy + +
- Phenotypic similarity 0.132 to OMIM:601894 Glomerulopathy with fibronectin deposits 2 + +
+
+
+
+
+
+ Variants contributing to score:
+
+
+
+
+ SPLICE_REGION_VARIANT
+ SNV
+ 2-215433325-T-C [0/1]
+
+
+ rs368265641
+
+
+
+
+
+
+
+ Exomiser ACMG:
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+
+ []
+
+
+
+ ClinVar:
+
+
+
+
+
+
+
+ UNCERTAIN_SIGNIFICANCE
+ (criteria provided, single submitter)
+
+
+
+ Variant score: 0.797
+ CONTRIBUTING VARIANT
+
+
+ -
+
- Transcripts: +
- + + FN1:ENST00000354785.11:c.414A>G:p.(=) + + +
+
+
+ -
+
- Pathogenicity Data: + +
- No + pathogenicity data + + +
+
+
+ -
+
- Frequency Data: + +
- 1000Genomes: 0.0156% +
- TOPMed: 0.0008% +
- ExAC EAS: 0.0231% +
- gnomAD_E_EAS: 0.0232% +
- gnomAD_E_SAS: 0.0032% +
- gnomAD_G_NFE: 0.0067% +
+
+About
++ The Exomizer is a Java program that functionally annotates variants from whole-exome + sequencing data starting from a VCF file (version 4). The functional annotation code is + based on Jannovar and uses + UCSC KnownGene transcript definitions and + hg19 genomic coordinates +
++ Variants are prioritized according to user-defined criteria on variant frequency, pathogenicity, + quality, inheritance pattern, and model organism phenotype data. Predicted pathogenicity data + was extracted from the dbNSFP resource. +
++ Developed by the Computational Biology and Bioinformatics group at the + Institute for Medical Genetics and Human Genetics of the + Charité - Universitätsmedizin Berlin, the Mouse + Informatics Group at the Sanger Institute and the Smedley group at + Queen Mary University of London. +
+ + +Problems, suggestions, or comments? Please let us know
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