Submissions for variant NM_152564.5(VPS13B):c.2934+14A>T

gnomAD frequency: 0.00690  dbSNP: rs187151724

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000293425	SCV000470786	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000293425	SCV000743187	benign	Cohen syndrome	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000293425	SCV000744230	benign	Cohen syndrome	2017-05-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781921	SCV000920343	benign	not specified	2017-09-18	criteria provided, single submitter	clinical testing	Variant summary: c.2934+14A>T in VPS13B gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0114 (1356/118948 chrs tested, including 23 homozygotes), predominantly in individuals of South Asian descent (0.036; 594/16406 chrs tested). The observed frequency greatly exceeds the maximum expected allele frequency for a pathogenic variant of 0.0025, suggesting that it is likely to be a common polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but is cited as Likely Benign by reputable database/clinical laboratory. Taking together, the variant was classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000293425	SCV001731833	benign	Cohen syndrome	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001712763	SCV001946055	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001712763	SCV005267272	benign	not provided		criteria provided, single submitter	not provided