ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6566dup (p.Asn2189fs) (rs397507373)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
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) RCV000031635 SCV000301067 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000122925 SCV000166183 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn2189Lysfs*8) 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 not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 38053). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000160303 SCV000210784 pathogenic not provided 2017-09-22 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.6566dupA at the cDNA level and p.Asn2189LysfsX8 (N2189KfsX8) at the protein level. The normal sequence, with the base that is duplicated in brackets, is TAAAA[dupA]CGTA. The duplication causes a frameshift which changes an Asparagine to a Lysine at codon 2189, and creates a premature stop codon at position 8 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Ambry Genetics RCV000214634 SCV000273753 pathogenic Hereditary cancer-predisposing syndrome 2018-05-04 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160303 SCV000296613 pathogenic not provided 2015-09-24 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031635 SCV000327463 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000214634 SCV000905020 pathogenic Hereditary cancer-predisposing syndrome 2018-06-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031635 SCV000054242 pathogenic Breast-ovarian cancer, familial 2 2012-02-29 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.