ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4594_4598del (p.Val1532fs) (rs879254138)

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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) RCV000661551 SCV000783843 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 RCV000235317 SCV000293613 pathogenic not provided 2015-11-23 criteria provided, single submitter clinical testing This deletion of 5 nucleotides in BRCA2 is denoted c.4594_4598delGTTAA at the cDNA level and p.Val1532AsnfsX14(V1532NfsX14) at the protein level. The normal sequence, with the bases that are deleted in braces, is GAAAAAA[GTTAA]AATT. The deletion causes a frameshift, which changes a Valine to an Asparagine at codon 1532, and creates a premature stop codon at position 14 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. Based on the currently available information, we consider this deletion to be a pathogenic variant.
Invitae RCV000536128 SCV000635388 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1532Asnfs*14) 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: 246173). 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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