ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.964-2A>C

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Total submissions: 1
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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.

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