ClinVar Miner

Submissions for variant NM_033305.3(VPS13A):c.6541G>A (p.Val2181Ile)

gnomAD frequency: 0.00017  dbSNP: rs146158125
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000861596 SCV001001962 likely benign not provided 2024-01-25 criteria provided, single submitter clinical testing
GeneDx RCV000861596 SCV001767751 likely benign not provided 2021-03-31 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003396496 SCV004122220 uncertain significance not specified 2023-10-26 criteria provided, single submitter clinical testing Variant summary: VPS13A c.6541G>A (p.Val2181Ile) results in a conservative amino acid change located in the Vacuolar protein sorting-associated protein 13, VPS13 adaptor binding domain (IPR009543) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 251296 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in VPS13A causing Choreoacanthocytosis (0.00033 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.6541G>A in individuals affected with Choreoacanthocytosis and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as likely benign (n=2) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences RCV003908162 SCV004719037 likely benign VPS13A-related disorder 2019-07-30 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics RCV004029300 SCV004978102 likely benign Inborn genetic diseases 2022-03-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV001274101 SCV001457845 uncertain significance Chorea-acanthocytosis 2020-01-24 no assertion criteria provided clinical testing

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