ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4409_4410del (p.Ile1470fs) (rs80359446)

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
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113300 SCV000300741 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 RCV000564465 SCV000668524 pathogenic Hereditary cancer-predisposing syndrome 2017-01-26 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)
Color RCV000564465 SCV000683618 pathogenic Hereditary cancer-predisposing syndrome 2017-05-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781145 SCV000919009 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4409_4410delTA (p.Ile1470LysfsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.4415_4418delAGAA, p.Lys1472fsX6; c.4456_4459delGTTA, p.Val1486fsX5 ). The variant allele was found at a frequency of 4.1e-06 in 243686 control chromosomes (gnomAD). c.4409_4410delTA has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Konstantopoulou_2008, Movassagh_2017, van der Hout_2006). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113300 SCV000146418 pathogenic Breast-ovarian cancer, familial 2 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.