ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.3386A>G (p.Lys1129Arg)

gnomAD frequency: 0.00451  dbSNP: rs61759485
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000081892 SCV000113827 benign not specified 2013-04-30 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000081892 SCV000249406 likely benign not specified 2016-11-22 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000081892 SCV000297278 likely benign not specified 2015-11-10 criteria provided, single submitter clinical testing
GeneDx RCV000512666 SCV000512677 benign not provided 2019-07-17 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 19006247, 27353947, 28559085)
CeGaT Center for Human Genetics Tuebingen RCV000512666 SCV000609316 likely benign not provided 2022-02-01 criteria provided, single submitter clinical testing
Invitae RCV001079908 SCV000630870 benign Cohen syndrome 2021-12-18 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000512666 SCV000841635 likely benign not provided 2018-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000718361 SCV000849223 benign History of neurodevelopmental disorder 2018-11-28 criteria provided, single submitter clinical testing General population or sub-population frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign) ;Sub-population frequency in support of benign classification (not ava blue, manual h-w)
Illumina Laboratory Services,Illumina RCV001079908 SCV001322033 likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genome-Nilou Lab RCV001079908 SCV001716386 likely benign Cohen syndrome 2021-05-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000081892 SCV002547503 benign not specified 2022-05-10 criteria provided, single submitter clinical testing Variant summary: VPS13B c.3386A>G (p.Lys1129Arg) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0046 in 251224 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 1.9 fold of the estimated maximal expected allele frequency for a pathogenic variant in VPS13B causing Cohen Syndrome phenotype (0.0025), strongly suggesting that the variant is benign. To our knowledge, no penetrant association of c.3386A>G in individuals affected with Cohen Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc. RCV001079908 SCV001456263 benign Cohen syndrome 2020-01-06 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000512666 SCV001917361 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000081892 SCV001953776 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000512666 SCV001975186 likely benign not provided no assertion criteria provided clinical testing

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