Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001346789 | SCV001541015 | likely pathogenic | Gorlin syndrome; Medulloblastoma | 2021-10-27 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individuals with clinical features of Gorlin syndrome (PMID: 29356994; 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in skipping of exon 11, but is expected to preserve the integrity of the reading-frame (PMID: 29356994). ClinVar contains an entry for this variant (Variation ID: 1042780). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 11 of the SUFU gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. |