ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2830A>T (p.Lys944Ter) (rs80358533)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131101 SCV000186031 pathogenic Hereditary cancer-predisposing syndrome 2017-09-06 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)
Baylor Genetics RCV000044070 SCV000540994 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077287 SCV000146122 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131101 SCV000292148 pathogenic Hereditary cancer-predisposing syndrome 2015-06-15 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077287 SCV000326771 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077287 SCV000677672 pathogenic Breast-ovarian cancer, familial 2 2015-08-11 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077287 SCV000744431 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000077287 SCV000605671 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077287 SCV000733241 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077287 SCV000300563 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000212222 SCV000210293 pathogenic not provided 2018-06-28 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2830A>T at the cDNA level and p.Lys944Ter (K944X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA) and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA2 3058A>T by alternate nomenclature, has been reported in multiple individuals with personal and/or family history of breast, ovarian, and/or pancreatic cancer (Hakansson 1997, Peto 1999, Capalbo 2006, Thomassen 2008, Borg 2010, Blay 2013, Lucas 2014). Additionally, Ruud et al. (2001) reported a patient with Fanconi anemia who passed away following a diagnosis of medulloblastoma and resultant chemotherapy toxicity. Follow-up studies on archived tissue by Bodd et al. (2010) revealed compound heterozygosity for BRCA2 Lys944Ter, present in her mother who had a family history of breast and ovarian cancer, and a BRCA2 missense variant, present in her father. We consider this variant to be pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785217 SCV000923785 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000496649 SCV000694634 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-13 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2830A>T (p.Lys944X) 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 and other laboratories (e.g. c.2287delC, c.2400_2401delTA, c.2808delA, etc.). This variant is absent in 120672 control chromosomes from ExAC. This variant is widely reported as a pathogenic variant in literature and clinical databases and has been reported in several HBOC patients/families, including evidence of cosegregation. In addition, this variant has also been reported in a patient with Fanconi Anemia (Bodd_2010). Several clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.
Mendelics RCV000496649 SCV000838779 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212222 SCV000296716 pathogenic not provided 2015-03-04 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496649 SCV000587645 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077287 SCV000109084 pathogenic Breast-ovarian cancer, familial 2 2006-11-27 no assertion criteria provided clinical testing

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