ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2471T>G (p.Leu824Ter) (rs397507631)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000257389 SCV000326710 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000257389 SCV000324080 pathogenic Breast-ovarian cancer, familial 2 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000506370 SCV000617464 pathogenic not provided 2017-10-06 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2471T>G at the cDNA level and p.Leu824Ter (L824X) at the proteinlevel. Using alternate nomenclature, this variant would be defined as BRCA2 2699T>G. The substitution creates anonsense variant, which changes a Leucine to a premature stop codon (TTA>TGA), and is predicted to cause loss ofnormal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has beenreported as a pathogenic variant in one French family, however, no clinical information was provided (Lecarpentier2012). Based on currently available information, we consider this variant to be pathogenic
Invitae RCV000044003 SCV000072016 pathogenic Hereditary breast and ovarian cancer syndrome 2016-02-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 824 (p.Leu824*) 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, truncating variants in BRCA2 are known to be pathogenic (PMID: 20104584). A different variant (c.2471_2476delTAAATG) giving rise to the same protein effect observed here (p.Leu824*) has been reported in a patient affected with breast cancer (PMID: 15858120). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506370 SCV000600513 pathogenic not provided 2017-05-04 criteria provided, single submitter 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.