ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.267G>A (p.Pro89=) (rs587780648)

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Total submissions: 11
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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) RCV000169543 SCV000578711 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/).
Invitae RCV000122903 SCV000166161 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000124002 SCV000167402 benign not specified 2013-12-05 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 RCV000164022 SCV000214627 likely benign Hereditary cancer-predisposing syndrome 2014-08-29 criteria provided, single submitter clinical testing
Counsyl RCV000169543 SCV000221032 likely benign Breast-ovarian cancer, familial 2 2015-01-15 criteria provided, single submitter literature only
Illumina Clinical Services Laboratory,Illumina RCV000264473 SCV000383606 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000122903 SCV000383607 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000124002 SCV000591670 benign not specified 2012-11-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000859023 SCV000600520 likely benign not provided 2018-10-23 criteria provided, single submitter clinical testing
Color RCV000164022 SCV000683497 likely benign Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000124002 SCV000694616 likely benign not specified 2018-12-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.267G>A 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 3.2e-05 in 277136 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.267G>A has been reported in the literature in individuals affected with Hereditary Breast and/or Ovarian Cancer without strong evidence for causality (Zuntini_2018, Borg_2010). Co-occurrences with other pathogenic variants have been reported in our internal and also, external databases (BRCA1 c.212+1G>A; BRCA2 c.5782G>T, p.Glu1928X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions from clinical diagnostic laboratories and reputable databases (evaluation after 2014) cite the variant as likely benign (5x) and once as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

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