ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7757G>A (p.Trp2586Ter) (rs80359003)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131087 SCV000186017 pathogenic Hereditary cancer-predisposing syndrome 2017-06-09 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000077410 SCV000147172 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000131087 SCV000537635 pathogenic Hereditary cancer-predisposing syndrome 2016-07-11 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077410 SCV000327724 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045302 SCV000592139 pathogenic Hereditary breast and ovarian cancer syndrome 2013-04-05 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000045302 SCV000588116 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077410 SCV000282448 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735604 SCV000863742 pathogenic Breast and/or ovarian cancer 2015-07-13 no assertion criteria provided clinical testing
GeneDx RCV000215688 SCV000278876 pathogenic not provided 2018-09-13 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.7757G>A at the cDNA level and p.Trp2586Ter (W2586X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as BRCA2 7985G>A using alternate nomenclature, has been reported in association with breast, ovarian, and prostate cancer (Perkowska 2003, Jonsson 2005, George 2013, Walker 2014), and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000045302 SCV000695098 pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-20 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7757G>A (p.Trp2586X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. If a protein product is made, it is predicted to truncate the tower domain, Nucleic acid-binding, OB-fold domain, helical domain, and oligonucleotide/ oligosaccharide-binding 3 (InterPro). Truncations at this position or downstream of this position have been classified as pathogenic by our laboratory (e.g. c.7758G>A/p.Trp2586X, p.Arg2645fsX3, p.Arg2892fsX14, etc.). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 121352 control chromosomes, but has been reported in multiple HBOC and prostate cancer patients in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000045302 SCV000073315 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 2586 (p.Trp2586*). It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in families and individuals with hereditary breast and ovarian cancer (PMID: 11802209, 16528604, 23633455, 12673801) and in individuals with prostate cancer (PMID: 23569316, 23035815, 25485004). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000215688 SCV000600767 pathogenic not provided 2016-07-01 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045302 SCV000587905 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077410 SCV000109208 pathogenic Breast-ovarian cancer, familial 2 2013-04-11 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.