Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000259933 | SCV000332301 | uncertain significance | not provided | 2018-08-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002317798 | SCV000850728 | likely benign | Inborn genetic diseases | 2024-01-02 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV001828180 | SCV002815345 | uncertain significance | Smith-Lemli-Opitz syndrome | 2024-02-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001828180 | SCV002993557 | uncertain significance | Smith-Lemli-Opitz syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 367 of the DHCR7 protein (p.Arg367Cys). This variant is present in population databases (rs531038145, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with DHCR7-related conditions. ClinVar contains an entry for this variant (Variation ID: 281496). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155146 | SCV003844870 | uncertain significance | not specified | 2023-02-16 | criteria provided, single submitter | clinical testing | Variant summary: DHCR7 c.1099C>T (p.Arg367Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 248618 control chromosomes, predominantly at a frequency of 0.0019 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in DHCR7 causing Smith-Lemli-Opitz Syndrome (0.00019 vs 0.0043), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1099C>T in individuals affected with Smith-Lemli-Opitz Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Natera, |
RCV001828180 | SCV002093009 | uncertain significance | Smith-Lemli-Opitz syndrome | 2017-10-17 | no assertion criteria provided | clinical testing |