Submissions for variant NM_152564.5(VPS13B):c.1981G>A (p.Asp661Asn)

gnomAD frequency: 0.00049  dbSNP: rs149334616

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000370221	SCV000334298	uncertain significance	not provided	2015-09-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317803	SCV000850348	uncertain significance	Inborn genetic diseases	2021-03-19	criteria provided, single submitter	clinical testing	The c.1981G>A (p.D661N) alteration is located in exon 14 (coding exon 13) of the VPS13B gene. This alteration results from a G to A substitution at nucleotide position 1981, causing the aspartic acid (D) at amino acid position 661 to be replaced by an asparagine (N). The p.D661N alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Invitae	RCV000818259	SCV000958860	benign	Cohen syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000818259	SCV001320457	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.
GeneDx	RCV000370221	SCV001782569	uncertain significance	not provided	2023-09-08	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
PreventionGenetics, part of Exact Sciences	RCV003391032	SCV004119367	uncertain significance	VPS13B-related disorder	2024-02-21	criteria provided, single submitter	clinical testing	The VPS13B c.1981G>A variant is predicted to result in the amino acid substitution p.Asp661Asn. This variant has been reported in the heterozygous state in a cohort study of very early onset inflammatory bowel disease (VEO-IBD) (Kelsen et al. 2015. PubMed ID: 26193622, Supplementary Table 2). However, no additional studies were performed to help assess the pathogenicity of this variant. This variant is reported in 0.067% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which is likely too common to be 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.
Natera, Inc.	RCV000818259	SCV001456247	likely benign	Cohen syndrome	2020-04-15	no assertion criteria provided	clinical testing