ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8489G>A (p.Trp2830Ter) (rs80359101)

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Total submissions: 7
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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) RCV000077442 SCV000301423 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000222775 SCV000271335 pathogenic Hereditary breast and ovarian cancer syndrome 2015-03-23 criteria provided, single submitter clinical testing The p.Trp2830X variant in BRCA2 has not been previously reported in individuals with cancer or in large population studies. This nonsense variant leads to a pre mature termination codon at position 2830, which is predicted to lead to a trunc ated or absent protein. Heterozygous loss of BRCA2 function is an established di sease mechanism in BRCA2-associated cancers. In summary, the p.Trp2830X variant is pathogenic for BRCA2-associated cancers in an autosomal dominant manner (http ://www.partners.org/personalizedmedicince/LMM) based upon its predicated impact to the protein and absence in controls.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077442 SCV000327909 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000484831 SCV000572118 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8489G>A at the cDNA level and p.Trp2830Ter (W2830X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 8717G>A. 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. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Ambry Genetics RCV000569959 SCV000661164 pathogenic Hereditary cancer-predisposing syndrome 2016-03-24 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)
Sharing Clinical Reports Project (SCRP) RCV000077442 SCV000109240 pathogenic Breast-ovarian cancer, familial 2 2010-10-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077442 SCV000147383 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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