Submissions for variant NM_152564.5(VPS13B):c.11656G>A (p.Val3886Ile)

gnomAD frequency: 0.00016  dbSNP: rs141793014

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000154134	SCV000203798	uncertain significance	not provided	2014-01-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000701453	SCV000830254	likely benign	Cohen syndrome	2024-01-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000701453	SCV001322583	uncertain significance	Cohen syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV003343661	SCV004066879	likely benign	Inborn genetic diseases	2023-08-02	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.
PreventionGenetics, part of Exact Sciences	RCV003390846	SCV004118713	uncertain significance	VPS13B-related disorder	2023-11-29	criteria provided, single submitter	clinical testing	The VPS13B c.11656G>A variant is predicted to result in the amino acid substitution p.Val3886Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.056% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV000154134	SCV004158287	uncertain significance	not provided	2022-08-01	criteria provided, single submitter	clinical testing	VPS13B: PM2, BP4
Natera, Inc.	RCV000701453	SCV001454489	uncertain significance	Cohen syndrome	2020-04-15	no assertion criteria provided	clinical testing