ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9838C>T (p.Pro3280Ser) (rs55835607)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045903 SCV000073916 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000487013 SCV000566872 uncertain significance not provided 2018-12-21 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9838C>T at the cDNA level, p.Pro3280Ser (P3280S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). Using alternate nomenclature, this variant would be defined as BRCA2 10066C>T. This variant showed complementation and homology directed repair capacity similar to wild type and did not significantly impact sensitivity to DNA damaging agents in in vitro functional studies (Mesman 2018). BRCA2 Pro3280Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). BRCA2 Pro3280Ser is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Pro3280Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000509955 SCV000607793 likely benign Hereditary cancer-predisposing syndrome 2020-02-28 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Color Health, Inc RCV000509955 SCV000684093 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193233 SCV001361958 likely benign not specified 2019-01-08 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9838C>T (p.Pro3280Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 246060 control chromosomes. 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.9838C>T in individuals affected with Hereditary Breast and Ovarian Cancer has been reported. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.5145delC, BIC; BRCA2 c.755_758delACAG, UMD), providing supporting evidence for a benign role. A mouse embryonic stem cell (mESC)-based functional assay showed the variant to have proper complementation to loss of endogenous Brca2 and 125% HDR capacity compared to wild-type (Mesman_2018). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Sharing Clinical Reports Project (SCRP) RCV000077476 SCV000109274 likely benign Breast-ovarian cancer, familial 2 2010-09-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077476 SCV000145718 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 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.