ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5193_5194TC[2] (p.Ser1733fs) (rs876660228)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218209 SCV000277472 pathogenic Hereditary cancer-predisposing syndrome 2015-08-03 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000661529 SCV000783819 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 RCV000657265 SCV000778996 pathogenic not provided 2016-11-21 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.5197_5198delTC at the cDNA level and p.Ser1733ArgfsX9 (S1733RfsX9) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCTC[delTC]CGAA. The deletion causes a frameshift which changes a Serine to an Arginine at codon 1733, and creates a premature stop codon at position 9 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000700708 SCV000829475 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1733Argfs*9) 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 a family with an increasing risk of breast and ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 233155). 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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