ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.67+1G>T (rs81002796)

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 RCV000162894 SCV000213381 pathogenic Hereditary cancer-predisposing syndrome 2017-07-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Functionally-validated splicing mutation,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Breast Cancer Information Core (BIC) (BRCA2) RCV000077382 SCV000146094 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Color RCV000162894 SCV000904689 pathogenic Hereditary cancer-predisposing syndrome 2015-03-03 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077382 SCV000327502 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045022 SCV000694986 pathogenic Hereditary breast and ovarian cancer syndrome 2016-04-26 criteria provided, single submitter clinical testing Variant summary: The variant of interest is located at a conserved intronic position that is known to affect splicing, with 4/5 in silico programs via Alamut predicting an affect on splicing, which is supported by a functional study, Houdayer_2012. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP) and has been reported via publications in affeced individuals. In addition, multiple reputable databases/clinical laboratories cite the variant with a classification of "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Invitae RCV000045022 SCV000073035 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a family affected with breast and/or ovarian cancer (PMID: 12938098). It is also known as IVS2+1G>T in the literature. ClinVar contains an entry for this variant (RCV000077382). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). Experimental studies have shown that this variant impacts splicing and results in the skipping of exon 2 in the BRCA2 mRNA (PMID: 22505045). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000505843 SCV000296749 pathogenic not provided 2015-01-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077382 SCV000109179 pathogenic Breast-ovarian cancer, familial 2 2011-09-29 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.