ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4310_4311GT[3] (p.Ala1439fs) (rs1064794168)

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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) RCV000661660 SCV000783962 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 RCV000485373 SCV000568045 pathogenic not provided 2015-09-22 criteria provided, single submitter clinical testing This duplication of 2 nucleotides in BRCA2 is denoted c.4312_4313dupGT at the cDNA level and p.Ala1439SerfsX10 (A1439SfsX10) at the protein level. The normal sequence, with the bases that are duplicated in braces, is TAGT[GT]CGCC. The duplication causes a frameshift, which changes an Alanine to a Serine at codon 1439, and creates a premature stop codon at position 10 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 RCV000542015 SCV000635356 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala1439Serfs*10) 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 not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 419879). 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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