ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8837T>A (p.Leu2946Ter) (rs431825371)

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
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000082995 SCV000301313 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000164349 SCV000214982 pathogenic Hereditary cancer-predisposing syndrome 2017-08-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000471016 SCV000549519 pathogenic Hereditary breast and ovarian cancer syndrome 2016-11-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 2946 (p.Leu2946*) of the BRCA2 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000508358 SCV000602756 pathogenic not specified 2016-08-12 criteria provided, single submitter clinical testing
Color RCV000164349 SCV000684001 pathogenic Hereditary cancer-predisposing syndrome 2016-11-04 criteria provided, single submitter clinical testing
GeneDx RCV000657681 SCV000779430 pathogenic not provided 2016-05-06 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8837T>A at the cDNA level and p.Leu2946Ter (L2946X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000082995 SCV000115069 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 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.