Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001004376 | SCV001163339 | pathogenic | Smith-Lemli-Opitz syndrome | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV001004376 | SCV001582052 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.His119Ilefs*8) in the DHCR7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DHCR7 are known to be pathogenic (PMID: 9634533, 10677299). This variant is present in population databases (rs747827699, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Smith–Lemli–Opitz syndrome (PMID: 15776424). ClinVar contains an entry for this variant (Variation ID: 813425). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001004376 | SCV002766162 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2022-11-28 | criteria provided, single submitter | clinical testing | Variant summary: DHCR7 c.355delC (p.His119IlefsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250946 control chromosomes. c.355delC has been reported in the literature in individuals affected with Smith-Lemli-Opitz Syndrome (Witsch-Baumgartner_2005). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV001004376 | SCV002813928 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-03-21 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001004376 | SCV002093061 | pathogenic | Smith-Lemli-Opitz syndrome | 2017-03-16 | no assertion criteria provided | clinical testing |