ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5653del (p.Cys1885fs) (rs886040602)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000576752 SCV000677898 likely pathogenic Breast-ovarian cancer, familial 2 2017-06-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000576752 SCV000783695 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000476395 SCV000918877 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-03 criteria provided, single submitter clinical testing Variant summary: The c.5653delT (p.Cys1885Alafs*24) variant in BRCA2 gene is a frameshift change that results in the loss of the ~1500 amino acids of BRCA2 protein (~55%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population datasets of ExAC and gnomAD (120680 and 244700 chrs tested, respectively). The c.5653delT has not, to our knowledge, been reported in affected individuals via published reports but is cited as Pathogenic by reputable databases/clinical laboratories. Other truncated variants, such as c.5656C>T (p.Gln1886* and c.5665delA (p.Ile1889Leufs*20), have been reported in association with HBOC. Taking together, the variant was classified as Likely Pathogenic.
Invitae RCV000476395 SCV000549617 pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-20 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 11 of the BRCA2 mRNA (c.5653delT), causing a frameshift at codon 1885. This creates a premature translational stop signal (p.Cys1885Alafs*24) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, 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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