ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1800T>G (p.Tyr600Ter) (rs80358464)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162912 SCV000213399 pathogenic Hereditary cancer-predisposing syndrome 2018-03-02 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) RCV000077266 SCV000145943 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000162912 SCV000905004 pathogenic Hereditary cancer-predisposing syndrome 2018-08-27 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077266 SCV000326615 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077266 SCV000300463 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 RCV000418517 SCV000517273 pathogenic not provided 2018-02-19 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.1800T>G at the cDNA level and p.Tyr600Ter (Y600X) at the protein level. Using alternate nomenclature, This variant would be defined as BRCA2 2028T>G. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAT>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not been published, another variant, published as BRCA2 2028T>A, results in the same nonsense variant Tyr600Ter and was observed in individuals with breast and/or ovarian cancer (Pal 2013, Tea 2014, Lynce 2015). Based on currently available information, this variant is considered pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000496768 SCV000605810 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-23 criteria provided, single submitter clinical testing The p.Tyr600X variant in BRCA2 has been reported in at least 3 individuals with BRCA2-associated cancers (Breast Cancer Information Core (BIC) database) and was absent from large population studies. This nonsense variant leads to a prematur e termination codon at position 600, which is predicted to lead to a truncated o r absent protein. Heterozygous loss of function of the BRCA2 gene is an establis hed disease mechanism in hereditary breast and ovarian cancer (HBOC). In additio n, this variant was classified as Pathogenic on September 8, 2016 by the ClinGen -approved ENIGMA expert panel (ClinVar SCV000300463.2). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon the predicted impact to the protein.
Michigan Medical Genetics Laboratories,University of Michigan RCV000077266 SCV000267747 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000418517 SCV000600489 pathogenic not provided 2017-03-07 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496768 SCV000587611 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077266 SCV000109063 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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