ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7946del (p.Pro2649fs) (rs863224828)

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Total submissions: 4
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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) RCV000241241 SCV000301222 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000196534 SCV000255256 pathogenic Hereditary breast and ovarian cancer syndrome 2015-06-06 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide in exon 17 of the BRCA2 mRNA (c.7946delC), causing a frameshift at codon 2649. This creates a premature translational stop signal (p.Pro2649Glnfs*8) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000241241 SCV000488601 likely pathogenic Breast-ovarian cancer, familial 2 2016-05-05 criteria provided, single submitter clinical testing
GeneDx RCV000480587 SCV000568871 pathogenic not provided 2016-10-05 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.7946delC at the cDNA level and p.Pro2649GlnfsX8 (P2649QfsX8) at the protein level. The normal sequence, with the base that is deleted in braces, is AGCC[C]AGAA. The deletion causes a frameshift, which changes a Proline to a Glutamine at codon 2649, and creates a premature stop codon at position 8 of the new reading frame. Although this variant, also defined as BRCA2 8174delC using alternate nomenclature, 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.

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