ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4320A>G (p.Lys1440=) (rs769535925)

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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 RCV000568638 SCV000661387 likely benign Hereditary cancer-predisposing syndrome 2016-12-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign,In silico models in agreement (benign)
Color RCV000568638 SCV000688868 likely benign Hereditary cancer-predisposing syndrome 2016-12-12 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495462 SCV000578671 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/).
Integrated Genetics/Laboratory Corporation of America RCV000507863 SCV000918954 uncertain significance not specified 2018-08-31 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4320A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.4e-06 in 238062 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4320A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign (3x) or VUS (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507863 SCV000600584 uncertain significance not specified 2017-05-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758893 SCV000887811 uncertain significance not provided 2017-05-25 criteria provided, single submitter clinical testing

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