Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000811047 | SCV000951293 | pathogenic | BAP1-related tumor predisposition syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 13 of the BAP1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BAP1 are known to be pathogenic (PMID: 21874000, 23684012). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with malignant mesothelioma (PMID: 26719535). ClinVar contains an entry for this variant (Variation ID: 654973). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 26719535). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002397665 | SCV002712512 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-05-05 | criteria provided, single submitter | clinical testing | The c.1729+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 13 of the BAP1 gene. In one study, this mutation was identified in an individual with mesothelioma that had a family history of mesothelioma and cutaneous melanoma. A mini-gene splicing assay, performed in this same study, indicated that the c.1729+1G>A mutant construct resulted in an abnormal transcript lacking exon 13 (Ohar JA et al. Cancer Res., 2016 Jan;76:206-15). In addition to the clinical data presented in the literature, 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 a disease-causing mutation. |