ClinVar Miner

Submissions for variant NM_004068.4(AP2M1):c.508C>T (p.Arg170Trp) (rs1577059692)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000850490 SCV001194272 likely pathogenic Intellectual developmental disorder 60 with seizures 2019-12-04 criteria provided, single submitter curation This variant is interpreted as Likely pathogenic for Intellectual developmental disorder 60 with seizures, autosomal dominant. The following ACMG Tag(s) were applied: PM2, PM6, PS3-Moderate, PS4-Supporting, PP3, PP2.
New York Genome Center RCV001263339 SCV001441380 pathogenic Autistic disorder of childhood onset; Seizures; Intellectual disability 2020-01-28 criteria provided, single submitter clinical testing The c.508C>T (p.Arg170Trp) variant identified in the AP2M1 gene substitutes a completely conserved Arginine for Tryptophan at amino acid 170/436 (coding exon 6/12). This variant is absent from gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms predict this variant to be Deleterious (Provean; score: -5.70) and Damaging (SIFT; score: 0.000) to the function of the canonical transcript. This variant is reported as Pathogenic in ClinVar (VarID:689722) based on literature evidence. The c.508C>T (p.Arg170Trp) variant has been identified de novo in 4 individuals with Intellectual Developmental Disorder with Seizures [PMID: 31104773]. Functional analysis of the p.Arg170Trp variant suggests it impairs clathrin dependent endocytosis, possibly via altered recognition potential of cargo membrane proteins [PMID: 31104773]. This variant was identified de novo in an individual submitted for clinical WGS testing. The c.508C>T (p.Arg170Trp) variant identified in the AP2M1 gene is reported here as Pathogenic.
OMIM RCV000850490 SCV000992685 pathogenic Intellectual developmental disorder 60 with seizures 2020-12-11 no assertion criteria provided literature only

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