ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7916C>T (p.Pro2639Leu) (rs774723315)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213138 SCV000274929 uncertain significance Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
Color RCV000213138 SCV000911810 likely benign Hereditary cancer-predisposing syndrome 2018-02-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000499513 SCV000592158 uncertain significance not specified 2014-10-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000499513 SCV000916954 uncertain significance not specified 2018-06-11 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7916C>T (p.Pro2639Leu) results in a non-conservative amino acid change located in the Breast cancer type 2 susceptibility protein, helical domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246060 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.7916C>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Deihimi_2017, Jakimovska_2018, Schenkel_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.5645C>A, p.Ser1882X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000199791 SCV000254216 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2639 of the BRCA2 protein (p.Pro2639Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs774723315, ExAC <0.01%). This variant has been observed in an individual with breast cancer (PMID: 29335924). ClinVar contains an entry for this variant (Variation ID: 216260). This variant has been reported not to substantially affect BRCA2 protein function (PMID: 29884841). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics RCV000679188 SCV000805770 uncertain significance not provided 2017-12-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679188 SCV000889138 uncertain significance not provided 2018-02-23 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000239039 SCV000297556 benign Breast-ovarian cancer, familial 2 2013-12-17 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.