ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7721G>A (p.Trp2574Ter) (rs80358997)

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Total submissions: 5
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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) RCV000077408 SCV000301198 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000416519 SCV000494419 pathogenic Hereditary breast and ovarian cancer syndrome 2015-08-12 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes a nonsense mutation resulting a truncated BRCA2 protein, a known mechanism for disease. The variant is located in close proximity to other pathogenic variants such as c.7719dupA (p.Leu2573TrpfsX), c.7738C>T (p.Gln2580X), and 7731delA (p.Gly2578GlufsX70),suggesting the variant is located in a mutational hotspot. The variant of interest has not been observed in affected individuals via publications. However, two reputable databases/clinical laboraties, BIC and SCRP cites the variant with a classification of "pathogenic." Therefore, taking the following lines of evidence into consideration: i) nonsense mutation resulting in a truncated BRCA2 protein, a known mechanism for disease, ii) not found in controls, ExAC, 1000 Gs and ESP, iii) located in a potential mutation hot spot, and iv) reputable databases/clinical laboratories classifying the variant as "pathogenic,". The variant of interest is classified as pathogenic.
GeneDx RCV000657751 SCV000779503 pathogenic not provided 2018-01-31 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7721G>A at the cDNA level and p.Trp2574Ter (W2574X) 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 protein truncation. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077408 SCV000109206 pathogenic Breast-ovarian cancer, familial 2 2009-06-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077408 SCV000147167 pathogenic Breast-ovarian cancer, familial 2 2001-03-30 no assertion criteria provided clinical testing

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