ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10250A>G (p.Tyr3417Cys) (rs730881600)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160263 SCV000210702 likely benign not specified 2016-02-24 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.
Invitae RCV000230091 SCV000283162 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-07-30 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 3417 of the BRCA2 protein (p.Tyr3417Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in in an individual with personal or family history of breast or ovarian cancer (PMID: 29161300). ClinVar contains an entry for this variant (Variation ID: 182306). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.
Color Health, Inc RCV000771295 SCV000903509 likely benign Hereditary cancer-predisposing syndrome 2016-12-16 criteria provided, single submitter clinical testing
Mendelics RCV000989096 SCV001139290 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160263 SCV001363361 uncertain significance not specified 2019-12-16 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.10250A>G (p.Tyr3417Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250062 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.10250A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Alemar_2017). This report however, does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=2) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.

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.