ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.631+1G>A (rs81002897)

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 RCV000044895 SCV000072908 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the BRCA2 gene. It is expected to disrupt RNA 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 observed on the opposite chromosome (in trans) from a pathogenic variant in two individuals affected with Fanconi anemia (FA) (PMID: 16825431, 15004464). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has also been reported in individuals affected with breast cancer (PMID: 27393621). This sequence change is also known as IVS7+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 9348). Experimental studies have shown that this sequence change results in the out-of-frame skipping of exon 7. This is expected to create a premature translational stop signal (p.Val211Serfs*19), resulting in an absent or disrupted protein product (PMID: 15004464). 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). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131851 SCV000186906 pathogenic Hereditary cancer-predisposing syndrome 2019-01-30 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rarity in general population databases (dbsnp, esp, 1000 genomes);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113913 SCV000327383 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000113913 SCV000677667 likely pathogenic Breast-ovarian cancer, familial 2 2017-02-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985563 SCV001133860 pathogenic not provided 2018-10-15 criteria provided, single submitter clinical testing The variant disrupts a canonical splice site, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. Assessment of experimental evidence suggests this variant results in abnormal protein function.
OMIM RCV000009942 SCV000030163 pathogenic Fanconi anemia, complementation group D1 2007-01-01 no assertion criteria provided literature only
Breast Cancer Information Core (BIC) (BRCA2) RCV000113913 SCV000147335 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 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.