Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000007192 | SCV001221466 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-12-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DHCR7 protein function. ClinVar contains an entry for this variant (Variation ID: 6790). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 11857552). 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 replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 280 of the DHCR7 protein (p.Tyr280Cys). |
| Prevention |
RCV003407291 | SCV004114551 | likely pathogenic | DHCR7-related disorder | 2023-01-12 | criteria provided, single submitter | clinical testing | The DHCR7 c.839A>G variant is predicted to result in the amino acid substitution p.Tyr280Cys. This variant was reported in the compound heterozygous state with a known pathogenic DHCR7 variant (c.964-1G>C) in an individual with Smith-Lemli-Opitz syndrome (SLOS) (Prasad et al. 2002. PubMed ID: 11857552). It was also reported in a study of Canadian SLOS patients, though no additional functional or genetic evidence was provided that could help clarify pathogenicity of the variant (Waye et al. 2002. PubMed ID: 12070263). The p.Tyr280 amino acid is located in a transmembrane domain (Nowaczyk. 2001. PubMed ID: 11453964) and suspected to be disruptive to the DHCR7 protein (Prasad et al. 2002. PubMed ID: 11857552). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. Taken together, this variant is interpreted as likely pathogenic. |
| OMIM | RCV000007192 | SCV000027388 | pathogenic | Smith-Lemli-Opitz syndrome | 2002-02-15 | no assertion criteria provided | literature only |