ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2426T>G (p.Leu809Ter) (rs397507285)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031367 SCV000300517 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 RCV000160047 SCV000210288 pathogenic not provided 2019-01-16 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2426T>G at the cDNA level and p.Leu809Ter (L809X) at the protein level. The substitution creates a nonsense variant, changing a Leucine to a premature stop codon (TTA>TGA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as 2654T>G using alternate nomenclature, has been reported in association with breast cancer (Claus 2005). We therefore consider this variant to be pathogenic.
Invitae RCV000204854 SCV000260063 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 809 (p.Leu809*) of the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in individuals with breast cancer and pancreatic cancer (PMID: 15728167, 26681312). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031367 SCV000296576 pathogenic Breast-ovarian cancer, familial 2 2016-01-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561108 SCV000661440 pathogenic Hereditary cancer-predisposing syndrome 2017-07-03 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)
Color RCV000561108 SCV000903409 pathogenic Hereditary cancer-predisposing syndrome 2017-02-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000204854 SCV000918826 pathogenic Hereditary breast and ovarian cancer syndrome 2017-10-05 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2426T>G (p.Leu809X) 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.2517C>A [p.Tyr839X] and c.2564_2565delCA [p.Thr855fsX25]). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 241082 control chromosomes, but has been identified in the literature in multiple affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031367 SCV000053972 pathogenic Breast-ovarian cancer, familial 2 2010-05-18 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000204854 SCV000587633 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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