ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7946del (p.Pro2649fs)

dbSNP: rs863224828
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Total submissions: 6
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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, susceptibility to, 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Labcorp Genetics (formerly Invitae), Labcorp RCV000196534 SCV000255256 pathogenic Hereditary breast ovarian cancer syndrome 2022-06-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro2649Glnfs*8) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 216857). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 30322717). This variant is not present in population databases (gnomAD no frequency).
Counsyl RCV000241241 SCV000488601 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 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.
Ambry Genetics RCV002415858 SCV002677975 pathogenic Hereditary cancer-predisposing syndrome 2020-08-07 criteria provided, single submitter clinical testing The c.7946delC pathogenic mutation, located in coding exon 16 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7946, causing a translational frameshift with a predicted alternate stop codon (p.P2649Qfs*8). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Baylor Genetics RCV004567440 SCV005058998 pathogenic Familial cancer of breast 2024-03-12 criteria provided, single submitter clinical testing

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