ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5277+2T>G

dbSNP: rs2051494815
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002348497 SCV002642631 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-25 criteria provided, single submitter clinical testing The c.5277+2T>G intronic variant results from a T to G substitution two nucleotides after coding exon 18 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 donor 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.
Revvity Omics, Revvity RCV003132218 SCV003809757 pathogenic not provided 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005093389 SCV005746075 pathogenic Hereditary breast ovarian cancer syndrome 2025-01-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 19 of the BRCA1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 865231). Studies have shown that disruption of this splice site results in activation of a cryptic splice site in intron 19 or skipping of exon 19 (also known as exon 20), and produces a non-functional protein and/or introduces a premature termination codon (PMID: 24667779; internal data). For these reasons, this variant has been classified as Pathogenic.
Brotman Baty Institute, University of Washington RCV001072611 SCV001238026 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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