Submissions for variant NM_152564.5(VPS13B):c.2704A>G (p.Lys902Glu)

gnomAD frequency: 0.00074  dbSNP: rs149531438

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000323681	SCV000470781	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.
Genetic Services Laboratory, University of Chicago	RCV000500194	SCV000597882	uncertain significance	not specified	2017-01-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000323681	SCV000755413	likely benign	Cohen syndrome	2024-01-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000762534	SCV000892862	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	VPS13B: BP4
GeneDx	RCV000762534	SCV001887844	likely benign	not provided	2020-06-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: no PMID)
Ambry Genetics	RCV002436218	SCV002744893	likely benign	Inborn genetic diseases	2021-08-04	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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000323681	SCV004171505	uncertain significance	Cohen syndrome	2023-10-19	criteria provided, single submitter	clinical testing	The VPS13B c.2704A>G (p.Lys902Glu) missense change has a maximum subpopulation frequency of 0.13% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with Cohen syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Natera, Inc.	RCV000323681	SCV001456257	benign	Cohen syndrome	2019-12-31	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902404	SCV004737005	likely benign	VPS13B-related disorder	2021-05-19	no assertion criteria provided	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).