ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4354C>T (p.Gln1452Ter) (rs431825319)

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Total submissions: 3
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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) RCV000661657 SCV000783958 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000423930 SCV000517199 pathogenic not provided 2018-12-13 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.4354C>T at the cDNA level and p.Gln1452Ter (Q1452X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in a woman with triple negative breast cancer (Wong-Brown 2015) and is considered pathogenic.
Invitae RCV000792245 SCV000931526 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1452*) 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 observed in an individual affected with breast cancer (PMID: 25682074). ClinVar contains an entry for this variant (Variation ID: 379780). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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