ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2905+3A>T

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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 RCV002439744 SCV002751883 likely pathogenic Hereditary cancer-predisposing syndrome 2023-06-04 criteria provided, single submitter clinical testing The c.2905+3A>T intronic variant results from an A to T substitution 3 nucleotides after coding exon 18 in the BRIP1 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003775416 SCV004589515 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-02-18 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 1797494). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 19 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein. It affects a nucleotide within the consensus splice site.

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