ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4909del (p.Val1637fs)

dbSNP: rs1064794377
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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) RCV000661792 SCV000784110 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000485455 SCV000569004 pathogenic not provided 2015-12-11 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.4909delG at the cDNA level and p.Val1637LeufsX7 (V1637LfsX7) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 5137delG. The normal sequence, with the base that is deleted in braces, is GAAA[G]TTAA. The deletion causes a frameshift, which changes a Valine to a Leucine at codon 1637, and creates a premature stop codon at position 7 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001382279 SCV001580961 pathogenic Hereditary breast ovarian cancer syndrome 2024-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1637Leufs*7) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 420258). For these reasons, this variant has been classified as Pathogenic.

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