ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3689_3690del (p.Ser1230fs) (rs869312759)

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Total submissions: 4
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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) RCV000661629 SCV000783928 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
University of Washington Department of Laboratory Medicine,University of Washington RCV000210084 SCV000266040 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing
GeneDx RCV000485377 SCV000566857 pathogenic not provided 2016-01-25 criteria provided, single submitter clinical testing The c.3689_3690delCT deletion in the BRCA2 gene has not been reported previously as apathogenic variant nor as a benign variant, to our knowledge. The c.3689_3690delCT variant causes aframeshift starting with codon Serine 1230, changes this amino acid to a Tyrosine residue, and createsa premature Stop codon at position 2 of the new reading frame, denoted p.Ser1230TyrfsX2. Thisvariant is predicted to cause loss of normal protein function either through protein truncation ornonsense-mediated mRNA decay. The c.3689_3690delCT variant was not observed in approximately6,500 individuals of European and African American ancestry in the NHLBI Exome SequencingProject, indicating it is not a common benign variant in these populations. We interpretc.3689_3690delCT as a pathogenic variant.
Invitae RCV000823753 SCV000964623 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1230Tyrfs*2) 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 pediatric cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 224523). 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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