ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9633dup (p.Gly3212fs) (rs1555289805)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
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) RCV000661481 SCV000783764 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000480880 SCV000570557 likely pathogenic not provided 2016-06-06 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.9633dupA at the cDNA level and p.Gly3212ArgfsX10 (G3212RfsX10) at the protein level. The normal sequence, with the base that is duplicated in braces, is GTAC[A]GGAA. The duplication causes a frameshift which changes a Glycine to an Arginine at codon 3212, and creates a premature stop codon at position 10 of the new reading frame. While this variant is not expected to lead to nonsense-mediated decay, it is predicted to cause loss of normal protein function through protein truncation. BRCA2 c.9633dupA is expected to result in the loss of the nuclear localization signals 1 and 2 (NLS1/NLS2) and the Cyclin A and RAD51 binding domains (Esashi 2005, Borg 2010, Roy 2012). Using alternate nomenclature, this variant would be defined as BRCA2 9861dupA. This duplication has not, to our knowledge, been reported in the literature. Based on the currently available evidence, we consider BRCA2 c.9633dupA to be a likely pathogenic variant.

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.