ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2971_2983del (p.Asn991fs) (rs886040456)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
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) RCV000257381 SCV000324123 pathogenic Breast-ovarian cancer, familial 2 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000257381 SCV000326794 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000474640 SCV000549712 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn991Aspfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a patient with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 266730). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000509601 SCV000608149 pathogenic Hereditary cancer-predisposing syndrome 2017-09-05 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)
GeneDx RCV000657257 SCV000778987 pathogenic not provided 2018-08-03 criteria provided, single submitter clinical testing This deletion of 13 nucleotides in BRCA2 is denoted c.2971_2983del13 at the cDNA level and p.Asn991AspfsX3 (N991DfsX3) at the protein level. The surrounding sequence is CATG[del13]GACT. The deletion causes a frameshift which changes an Asparagine to an Aspartic Acid at codon 991, and creates a premature stop codon at position 3 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.2971_2983del13 has been observed in at least one individual with a Lynch syndrome-associated cancer and/or colon polyps (Yurgelun 2015). We consider this variant to be pathogenic.
Color RCV000509601 SCV000903586 pathogenic Hereditary cancer-predisposing syndrome 2017-10-24 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.