ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5752C>T (p.His1918Tyr) (rs80358803)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163008 SCV000213496 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077359 SCV000146689 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000163008 SCV000910732 benign Hereditary cancer-predisposing syndrome 2015-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000077359 SCV000220254 likely benign Breast-ovarian cancer, familial 2 2014-04-17 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000168582 SCV000591998 benign not specified 2016-01-06 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077359 SCV000244460 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000575
GeneDx RCV000168582 SCV000210619 likely benign not specified 2018-03-13 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.
Genetic Services Laboratory, University of Chicago RCV000168582 SCV000593719 likely benign not specified 2016-04-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000168582 SCV000694899 likely benign not specified 2019-04-19 criteria provided, single submitter clinical testing BRCA2 c.5752C>T (p.His1918Tyr) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251154 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (4.4e-05 vs 0.00075), allowing no conclusion about variant significance. c.5752C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer and also, prostate cancer (Ernst_2018, Lu_2015, Kote-Jarai_2011). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A co-occurrence with a pathogenic variant has been reported (LabCorp; BRCA2 c.5946delT, p.Ser1982fsX22), providing supporting evidence for a benign role. In addition, studies utilizing multifactorial likelihood models to assess the clinical significance of BRCA2 variants predict this variant to be neutral/not pathogenic (Lindor_2012, Easton_2007). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six submitters including one expert panel have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all have classified the variant as benign (n=2)/likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign until additional clinical and functional data become available.
Invitae RCV000044743 SCV000072756 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-03 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000168582 SCV000966583 uncertain significance not specified 2018-05-15 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
PreventionGenetics RCV000168582 SCV000301766 likely benign not specified criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000168582 SCV000600662 likely benign not specified 2017-03-24 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077359 SCV000109156 likely benign Breast-ovarian cancer, familial 2 2011-02-24 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.