ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5241_5242insTA (p.Ser1748Ter) (rs749980674)

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
Ambry Genetics RCV000509883 SCV000608179 pathogenic Hereditary cancer-predisposing syndrome 2016-06-20 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000241313 SCV000327186 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) RCV000241313 SCV000300853 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000657807 SCV000779562 pathogenic not provided 2018-09-06 criteria provided, single submitter clinical testing This insertion of two nucleotides is denoted BRCA2 c.5241_5242insTA at the cDNA level and p.Ser1748Ter (S1748X) at the protein level. The normal sequence, with the bases that are inserted in brackets, is TAAC[insTA]AGCT. The insertion creates a nonsense variant, which changes a Serine to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.5241_5242insTA, previously reported as BRCA2 5469_5470insTA or 5469insTA using alternate nomenclature, has been reported in association with breast cancer (Fackenthal 2012). We consider this variant to be pathogenic.
Invitae RCV000550517 SCV000635438 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1748*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs749980674, ExAC 0.01%). This variant has been reported in an individual affected with breast cancer (PMID: 22034289). ClinVar contains an entry for this variant (Variation ID: 254555). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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.