ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6662del (p.Asn2221fs) (rs1064794812)

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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) RCV000661774 SCV000784089 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 RCV000478891 SCV000569998 pathogenic not provided 2016-04-18 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.6662delA at the cDNA level and p.Asn2221ThrfsX8 (N2221TfsX8) at the protein level. Using alternate nomenclature, this variant may be defined as BRCA2 6890delA or 6659delA. The normal sequence, with the base that is deleted in braces, is GAAA[A]CTAC. The deletion causes a frameshift which changes an Asparagine to a Threonine at codon 2221, and creates a premature stop codon at position 8 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 BRCA2 c.6662delA to be pathogenic.
Invitae RCV000822038 SCV000962818 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn2221Thrfs*8) 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 BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 420953). 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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