ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4987-2A>C

dbSNP: rs397509212
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000226415 SCV000289814 pathogenic Hereditary breast ovarian cancer syndrome 2019-01-30 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 15 of the BRCA1 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 not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 240810). Experimental studies have shown that this variant disrupts mRNA splicing and/or protein function (PMID: 30209399). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001023367 SCV001185232 likely pathogenic Hereditary cancer-predisposing syndrome 2019-02-07 criteria provided, single submitter clinical testing The c.4987-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 15 in the BRCA1 gene. 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.
Brotman Baty Institute, University of Washington RCV001072941 SCV001238408 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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