ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6960G>A (p.Leu2320=) (rs373134168)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163878 SCV000214466 likely benign Hereditary cancer-predisposing syndrome 2014-10-30 criteria provided, single submitter clinical testing
Color RCV000163878 SCV000689014 likely benign Hereditary cancer-predisposing syndrome 2017-07-25 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000494754 SCV000579116 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 RCV000123988 SCV000167386 benign not specified 2014-04-28 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.
Integrated Genetics/Laboratory Corporation of America RCV000587322 SCV000695014 uncertain significance not provided 2016-04-01 criteria provided, single submitter clinical testing Variant summary: This c.6960G>A variant affects a non-conserved nucleotide and results in a synonymous mutation. Mutation Taster predicts a benign outcome and 5/5 in silico tools via Alamut predict no significant impact on splicing by this change. This variant was found in the large and broad cohorts of ExAC at an allele frequency of 0.0000253 which does not exceed the maximal expected allele frequency of a disease causing BRCA2 allele (0.0007503) in this gene; however, it could still be a rare polymorphism. The variant of interest has not been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Two clinical labs via ClinVar classify the variant as Benign/Likely Benign, without evidence to independently evaluate. UMD lists this variant in 2 individuals with classification of 3-UV without co-occurrence with deleterious variants. Considering all, since the variant does not change the protein sequence and is not located in a region known to affect splicing, it is likely in the benign spectrum. However, due to lack of clinical data and functional studies, the variant has currenty been classified as a VUS-possibly benign until more information becomes available.
Invitae RCV000465611 SCV000560422 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-13 criteria provided, single submitter clinical testing

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