ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7418G>A (p.Cys2473Tyr) (rs55924966)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132080 SCV000187144 likely benign Hereditary cancer-predisposing syndrome 2018-04-30 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;In silico models in agreement (benign);Other data supporting benign classification
Color RCV000132080 SCV000906935 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001192570 SCV001360797 uncertain significance not specified 2019-06-06 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7418G>A (p.Cys2473Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250980 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2837A>G has been reported in the literature in an individual affected with breast cancer, however without strong evidence for causality (Encinas_2018). Co-occurrences with another pathogenic BRCA2 variant have been reported (c.5454delA (p.Cys1820AlafsX20) in an internal sample and in the NHGRI BIC database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 (without evidence for independent evaluation), and classified the variant as likely benign (1x) or VUS (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113753 SCV000147078 uncertain significance Breast-ovarian cancer, familial 2 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.