ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8969G>A (p.Trp2990Ter) (rs80359148)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131050 SCV000185980 pathogenic Hereditary cancer-predisposing syndrome 2018-03-20 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) RCV000114025 SCV000147503 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000114025 SCV000301326 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 RCV000425086 SCV000516129 pathogenic not provided 2017-02-01 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.8969G>A at the cDNA level and p.Trp2990Ter (W2990X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), 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 9197G>A using alternate nomenclature, has been observed in at least three breast cancer patients (Borg 2010, Ellingson 2015, Pal 2015). Functional studies demonstrated that BRCA2 Trp2990Ter confers aberrant splicing (Acedo 2012). We consider this variant to be pathogenic.
Invitae RCV000637796 SCV000759275 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp2990*) 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 reported in individuals affected with breast cancer (PMID: 26296701, 26287763, 20104584). This variant is also known as 9197G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 126195). 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 RCV000425086 SCV000600835 pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000114025 SCV000189320 pathogenic Breast-ovarian cancer, familial 2 2010-01-21 no assertion criteria provided clinical testing

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