ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1670T>G (p.Leu557Ter) (rs80358452)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000212212 SCV000883504 pathogenic not provided 2018-04-20 criteria provided, single submitter clinical testing The BRCA2 c.1670T>G; p.Leu557Ter variant (rs80358452), also known as 1898T>G for traditional nomenclature, is reported in the literature in association with hereditary breast and ovarian cancer syndrome (Sermijn 2004), and is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 51170). This variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Sermijn E et al. The impact of proband mediated information dissemination in families with a BRCA1/2 gene mutation. J Med Genet. 2004 Mar;41(3):e23.
Ambry Genetics RCV000217402 SCV000275617 pathogenic Hereditary cancer-predisposing syndrome 2017-11-03 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) RCV000112952 SCV000145911 pathogenic Breast-ovarian cancer, familial 2 2000-06-12 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112952 SCV000326586 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000112952 SCV000489322 pathogenic Breast-ovarian cancer, familial 2 2016-09-19 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496933 SCV000591760 pathogenic Hereditary breast and ovarian cancer syndrome 2015-03-23 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112952 SCV000300453 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 RCV000212212 SCV000210275 pathogenic not provided 2018-04-02 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.1670T>G at the cDNA level and p.Leu557Ter (L557X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TGA), 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 1898T>G, has been observed in association with breast and/or ovarian cancer (Sermijn 2004), and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496933 SCV000694557 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-08 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1670T>G (p.Leu557X) 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. This variant is absent in 121056 control chromosomes. Multiple publications have cited the variant in affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212212 SCV000888991 pathogenic not provided 2017-09-12 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496933 SCV000587603 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000112952 SCV000297504 pathogenic Breast-ovarian cancer, familial 2 2011-10-31 no assertion criteria provided clinical testing

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