Submissions for variant NM_152564.5(VPS13B):c.2596G>A (p.Val866Ile)

gnomAD frequency: 0.00076  dbSNP: rs150185067

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224087	SCV000281217	likely benign	not provided	2015-06-15	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Illumina Laboratory Services, Illumina	RCV000303841	SCV000470778	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	RCV000503780	SCV000597881	uncertain significance	not specified	2017-05-26	criteria provided, single submitter	clinical testing
Invitae	RCV000303841	SCV000827451	likely benign	Cohen syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317747	SCV000850039	likely benign	Inborn genetic diseases	2023-09-14	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	RCV003390976	SCV004120139	uncertain significance	VPS13B-related disorder	2023-11-29	criteria provided, single submitter	clinical testing	The VPS13B c.2596G>A variant is predicted to result in the amino acid substitution p.Val866Ile. This variant has been reported as a polymorphism in individuals with Cohen syndrome (Seifert et al. 2006. PubMed ID: 16648375). This variant is reported in 0.12% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which is more common than expected for a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV000224087	SCV004158254	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000303841	SCV001456254	likely benign	Cohen syndrome	2020-06-04	no assertion criteria provided	clinical testing