Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000815482 | SCV000955938 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-12-02 | criteria provided, single submitter | clinical testing | 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: 658626). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 10814720, 16983147). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 284 of the DHCR7 protein (p.Phe284Leu). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002442731 | SCV002676747 | likely pathogenic | Inborn genetic diseases | 2017-10-18 | criteria provided, single submitter | clinical testing | The p.F284L variant (also known as c.852C>A), located in coding exon 6 of the DHCR7 gene, results from a C to A substitution at nucleotide position 852. The phenylalanine at codon 284 is replaced by leucine, an amino acid with highly similar properties. This variant was identified in a female infant with Hirschsprung disease, dysmorphic features including mild ptosis, short nose with anteverted nares, long philtrum, micrognathia, 2-3 toe syndactyly, and elevated 7-dehydrocholesterol levels; this variant was identified in conjunction with a second DHCR7 alteration (Yu H et al. Hum. Mol. Genet., 2000 May;9:1385-91; Mueller C et al. Am. J. Med. Genet. A, 2003 Nov;123A:100-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| OMIM | RCV000815482 | SCV000027391 | pathogenic | Smith-Lemli-Opitz syndrome | 2003-11-15 | no assertion criteria provided | literature only | |
| Natera, |
RCV000815482 | SCV002093024 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2021-02-08 | no assertion criteria provided | clinical testing |