ClinVar Miner

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

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131060 SCV000185990 pathogenic Hereditary cancer-predisposing syndrome 2017-05-23 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) RCV000031340 SCV000145942 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131060 SCV000905003 pathogenic Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031340 SCV000326614 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) RCV000031340 SCV000300462 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 RCV000216426 SCV000279312 pathogenic not provided 2018-12-04 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.1800T>A at the cDNA level and p.Tyr600Ter (Y600X) at the protein level. This variant has been previously reported as BRCA2 2028T>A using alternate nomenclature. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAT>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in families whose clinical histories are consistent with Hereditary Breast and Ovarian Cancer syndrome (Pal 2013, Tea 2014, Lance 2015). We consider this variant to be pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000031340 SCV000839917 pathogenic Breast-ovarian cancer, familial 2 2017-05-24 criteria provided, single submitter clinical testing This c.1800T>A (p.Tyr600*) variant in the BRCA2 gene has been reported in patients with breast cancer [PMID 26250392, 23320992]. This variant is predicted to create a non sense variant and a premature stop codon at amino acid position 600 of the BRCA2 protein. This variant is thus predicted to result in a loss of function of the protein. In addition, it has been classified as pathogenic in ClinVar by an expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/37759/). This variant is classified as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496257 SCV000694567 pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-09 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1800T>A (p.Tyr600X) 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. p.Glu1518fsX25, p.Thr1526fsX3, p.Tyr1655X, etc.). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 118492 control chromosomes, but has been cited in multiple HBOC patients in the literature. In addition, multiple clinical diagnostic laboratories classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000496257 SCV000814370 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr600*) 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 observed in several individuals affected with breast and/or ovarian cancer (PMID: 23320992, 24156927, 26250392). This variant is also known as T2028A or 2028T>A in the literature. ClinVar contains an entry for this variant (Variation ID: 37759). 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 RCV000216426 SCV000600488 pathogenic not provided 2016-11-28 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496257 SCV000587612 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031340 SCV000053945 pathogenic Breast-ovarian cancer, familial 2 2012-05-31 no assertion criteria provided clinical testing

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