ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.278C>T (p.Thr93Met) (rs80338853)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biochemistry Laboratory of CDMU,Chengde Medical University RCV000007185 SCV000899186 pathogenic Smith-Lemli-Opitz syndrome no assertion criteria provided case-control
Counsyl RCV000007185 SCV000677954 pathogenic Smith-Lemli-Opitz syndrome 2015-06-13 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000079651 SCV000230167 pathogenic not provided 2013-08-05 criteria provided, single submitter clinical testing
GeneDx RCV000079651 SCV000512799 pathogenic not provided 2018-02-05 criteria provided, single submitter clinical testing The T93M variant has been reported in several unrelated individuals with SLOS who were homozygous for T93M, or heterozygous for T93M and a second pathogenic variant in the DHCR7 gene (Fitzky et al., 1998; Krakowiak et al., 2000; Nowaczyk et al., 2004). The T93M variant has been reported to be a founder mutation in various Mediterranean populations and has been associated with a mild SLOS phenotype (Krakowiak et al., 2000; Nowaczyk et al., 2004).
GeneReviews RCV000007185 SCV000040849 pathologic Smith-Lemli-Opitz syndrome 2007-10-24 no assertion criteria provided curation Converted during submission to Pathogenic.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000007185 SCV000746859 likely pathogenic Smith-Lemli-Opitz syndrome 2017-12-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000007185 SCV000697855 pathogenic Smith-Lemli-Opitz syndrome 2017-03-30 criteria provided, single submitter clinical testing Variant summary: The DHCR7 c.278C>T (p.Thr93Met) variant involves the alteration of a conserved nucleotide and 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a damaging outcome for this variant. This variant was found in 3/109422 control chromosomes from ExAC at a frequency of 0.0000274, which does not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301). Published studies have reported this variant in patients with SLOS in homozygous as well as in compound heterozygous state with other likely pathogenic/pathogenic variants. It is a known common pathogenic variant with possible founder effect in Mediterranean region. This variant is located in one of the transmembrane domains and expression of this mutant in mammalian cells showed decreased expression, lower than 5% (Witsch-Baumgartner_2000). Multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000007185 SCV000630074 pathogenic Smith-Lemli-Opitz syndrome 2018-08-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 93 of the DHCR7 protein (p.Thr93Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is clearly defined as a Smith–Lemli–Opitz syndrome causative allele (PMID: 9653161, 10995508, 14981719, 10677299, 15776424, 10602371). It has been reported as a founder mutation in Mediterranean populations (PMID: 14981719, 15776424). ClinVar contains an entry for this variant (Variation ID: 6783). For these reasons, this variant has been classified as Pathogenic.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000454251 SCV000537962 likely pathogenic Abnormality of brain morphology criteria provided, single submitter research
OMIM RCV000007185 SCV000027381 pathogenic Smith-Lemli-Opitz syndrome 2012-06-01 no assertion criteria provided literature only

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