ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5682C>G (p.Tyr1894Ter) (rs41293497)

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Total submissions: 25
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Academic Department of Medical Genetics, University of Cambridge RCV000131121 SCV000992212 pathogenic Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter research Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity.
Ambry Genetics RCV000131121 SCV000186051 pathogenic Hereditary cancer-predisposing syndrome 2018-01-04 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031570 SCV000146669 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148424 SCV000190123 pathogenic Ovarian cancer 2014-06-01 no assertion criteria provided research
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000044719 SCV000586962 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-18 criteria provided, single submitter clinical testing
Color RCV000131121 SCV000683723 pathogenic Hereditary cancer-predisposing syndrome 2016-05-17 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031570 SCV000327264 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031570 SCV000677688 pathogenic Breast-ovarian cancer, familial 2 2015-09-29 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031570 SCV000744473 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031570 SCV000605682 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044719 SCV000591987 pathogenic Hereditary breast and ovarian cancer syndrome 2012-08-13 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000044719 SCV000588102 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031570 SCV000733270 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031570 SCV000282412 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 RCV000735572 SCV000863710 pathogenic Breast and/or ovarian cancer 2015-11-23 no assertion criteria provided clinical testing
Fulgent Genetics,Fulgent Genetics RCV000031570 SCV000575740 pathogenic Breast-ovarian cancer, familial 2 2015-10-27 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515199 SCV000611178 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3; Tracheoesophageal fistula 2017-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000160095 SCV000210363 pathogenic not provided 2018-05-18 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.5682C>G at the cDNA level and p.Tyr1894Ter (Y1894X) at the protein level. The substitution creates a nonsense variant, changing a Tyrosine to a premature stop codon (TAC>TAG). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as 5910C>G using alternate nomenclature, has been observed in association with hereditary breast, ovarian, and prostate cancer (Risch 2001, Pohlreich 2005, Edwards 2010, Tea 2014, Cini 2016, Fernandes 2016, Kim 2016). We consider this variant to be pathogenic.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000031570 SCV000743310 pathogenic Breast-ovarian cancer, familial 2 2014-10-08 criteria provided, single submitter clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785225 SCV000923793 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000044719 SCV000494385 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5682C>G (p.Tyr1894X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.6644_6647delACTC, c.6682dupG, c.6997_6998delGT, etc.). This variant is absent in 120576 control chromosomes from ExAC. This variant is a recurrent pathogenic mutation found in several HBOC patients/families and in individuals undergoing BRCA1/2 clinical testing. In compound heterozygous with another variant, it has also been reported to cause Fanconi Anemia. Several clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as a Disease Variant (or Pathogenic).
Invitae RCV000044719 SCV000072732 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1894*) 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 individuals affected with ovarian cancer, breast cancer, prostate cancer, and Fanconi anemia (PMID: 11179017, 15070707, 16168118, 18042939, 20736950). This variant is also known as 5910C>G in the literature. ClinVar contains an entry for this variant (Variation ID: 37989). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160095 SCV000296756 pathogenic not provided 2015-02-18 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044719 SCV000587792 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031570 SCV000054175 pathogenic Breast-ovarian cancer, familial 2 2012-07-19 no assertion criteria provided clinical testing

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