ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4977C>T (p.Ser1659=) (rs45484897)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495225 SCV000579051 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx RCV000160226 SCV000210610 benign not specified 2014-08-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000163195 SCV000213716 likely benign Hereditary cancer-predisposing syndrome 2014-10-09 criteria provided, single submitter clinical testing
Invitae RCV000195751 SCV000253020 benign Hereditary breast and ovarian cancer syndrome 2017-12-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160226 SCV000600617 likely benign not specified 2017-03-06 criteria provided, single submitter clinical testing
Color RCV000163195 SCV000683664 benign Hereditary cancer-predisposing syndrome 2015-12-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589985 SCV000694818 benign not provided 2016-09-02 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4977C>T (p.Ser1659Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant, and 5/5 in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. This variant was found in 14/118706 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0002136 (14/65542). This frequency is slightly less than the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting the variant could potentially be a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. Additionally, the variant of interest has only been reported, to our knowledge, in one publication suggesting it was a somatic occurrence in a cell line, although information is limited. Furthermore, multiple reputable clinical laboratories have cited the variant with a classification of "likely benign/benign." In addition, a reputable database cites the variant to co-occur with another potentially pathogenic BRCA2 variant, c.6515C>A (p.Ser2172X) and in two LabCorp specimens, one with BRCA1 (p.K653fs*47) and one with a CHEK2 (c.1100delC), both of which are pathogenic. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589985 SCV000887832 likely benign not provided 2018-04-11 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000163195 SCV000787934 likely benign Hereditary cancer-predisposing syndrome 2018-01-12 no assertion criteria provided clinical testing

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