Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003618388 | SCV004410705 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-10-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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 activation of a cryptic splice site and introduces a new termination codon (PMID: 9653161). However the mRNA is not expected to undergo nonsense-mediated decay. Disruption of this splice site has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 10814720, 10995508, 11427181, 23042628). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 8 of the DHCR7 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. |