ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2576-2A>G

dbSNP: rs869312763
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Department of Laboratory Medicine, University of Washington RCV000210117 SCV000266055 likely pathogenic Hereditary cancer-predisposing syndrome 2015-11-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000210117 SCV000673153 likely pathogenic Hereditary cancer-predisposing syndrome 2024-05-29 criteria provided, single submitter clinical testing The c.2576-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 18 in the BRIP1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000796090 SCV000935586 likely pathogenic Familial cancer of breast; Fanconi anemia complementation group J 2023-12-17 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 18 of the BRIP1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 224527). Studies have shown that disruption of this splice site results in skipping of exon 19, but is expected to preserve the integrity of the reading-frame (Invitae). 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.
Revvity Omics, Revvity RCV001781630 SCV002022085 likely pathogenic Fanconi anemia complementation group J 2019-04-19 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003335229 SCV004044940 likely pathogenic Familial cancer of breast 2023-06-07 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Baylor Genetics RCV003335229 SCV004217095 likely pathogenic Familial cancer of breast 2023-06-02 criteria provided, single submitter clinical testing

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