Submissions for variant NM_152564.5(VPS13B):c.7801G>A (p.Glu2601Lys)

gnomAD frequency: 0.00006  dbSNP: rs144350008

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000324644	SCV000340483	likely benign	not specified	2016-03-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081640	SCV000755425	likely benign	Cohen syndrome	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000658165	SCV000779936	uncertain significance	not provided	2018-05-17	criteria provided, single submitter	clinical testing	The E2626K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E2626K variant is observed in 87/18830 (0.5%) alleles from individuals of East Asian background (Lek et al., 2016). The E2626K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Laboratory Services, Illumina	RCV001081640	SCV001324021	likely benign	Cohen syndrome	2018-01-12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
PreventionGenetics, part of Exact Sciences	RCV003909990	SCV004718625	likely benign	VPS13B-related disorder	2022-03-01	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).