ClinVar Miner

Submissions for variant NM_033305.3(VPS13A):c.6283del (p.Ser2095fs)

dbSNP: rs1587612257
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000826154 SCV000967689 pathogenic Chorea-acanthocytosis 2018-09-26 criteria provided, single submitter clinical testing The p.Ser2095GlnfsX10 variant in VPS13A has been reported in one individual with chorea-acanthocytosis in the compound heterozygote state (phase not confirmed) with another loss of function variant (Dobson-Stone 2002). It was absent from la rge population studies. This variant is predicted to cause a frameshift, which a lters the protein?s amino acid sequence beginning at position 2095 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the VPS 13A gene is an established disease mechanism in autosomal recessive chorea-acant hocytosis. In summary, this variant meets criteria to be classified as pathogeni c for autosomal recessive chorea-acanthocytosis based on case observations, abse nce from controls, and predicted impact on protein. ACMG/AMP criteria applied: P VS1, PM2, PM3_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002538244 SCV003264605 pathogenic not provided 2024-02-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser2095Glnfs*10) in the VPS13A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13A are known to be pathogenic (PMID: 12404112, 21598378). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with choreoacanthocytosis (PMID: 12404112). ClinVar contains an entry for this variant (Variation ID: 667398). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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