ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6938-1G>A (rs886040936)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258239 SCV000327541 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000801410 SCV000941184 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-08 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 12 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with male breast cancer (PMID: 28008555). ClinVar contains an entry for this variant (Variation ID: 267667). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mendelics RCV000258239 SCV001139163 likely pathogenic Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001025818 SCV001188080 likely pathogenic Hereditary cancer-predisposing syndrome 2019-03-31 criteria provided, single submitter clinical testing The c.6938-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 12 of the BRCA2 gene. This variant has been detected in a Romanian breast cancer family (Negura L et al. Revista Romana de Medicina de Laborator. 2012 Dec;20(4):317-26). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

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