ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2906-2A>C

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002439757 SCV002750927 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-12 criteria provided, single submitter clinical testing The c.2906-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 19 in the BRIP1 gene. This alteration occurs at the 3' terminus of the BRIP1 gene and is not expected to trigger nonsense-mediated mRNA decay. The exact functional effect of this alteration is unknown. In one study, this alteration was identified in 4/13213 breast cancer cases and in 2/5242 controls from the United Kingdom (Easton DF et al. J Med Genet, 2016 05;53:298-309). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003102861 SCV003512725 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2022-10-02 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 19 of the BRIP1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted 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 BRIP1-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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