Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002899389 | SCV003242732 | uncertain significance | BAP1-related tumor predisposition syndrome | 2022-10-25 | criteria provided, single submitter | clinical testing | 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. This variant has not been reported in the literature in individuals affected with BAP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the BAP1 gene. It does not directly change the encoded amino acid sequence of the BAP1 protein. |
Ambry Genetics | RCV004065953 | SCV005023382 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-10-11 | criteria provided, single submitter | clinical testing | The c.932-10C>G intronic variant results from a C to G substitution 10 nucleotides upstream from coding exon 11 in the BAP1 gene. This nucleotide position is not well conserved in available vertebrate species. This variant has been observed in at least one individual with a personal and/or family history that is consistent with BAP1-associated disease (Ambry internal data). This alteration was non-functional in a high throughput genome editing haploid cell survival assay (Waters AJ et al. Nat Genet 2024 Jul;56(7):1434-1445). In silico splice site analysis predicts that this alteration may weaken the native splice acceptor 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. |