ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.151C>T (p.Pro51Ser) (rs104886035)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000079646 SCV000230166 pathogenic not provided 2013-03-18 criteria provided, single submitter clinical testing
GeneDx RCV000079646 SCV000491237 pathogenic not provided 2018-06-13 criteria provided, single submitter clinical testing The P51S missense variant in the DHCR7 gene has been reported many times in patients with SLOS, and in one report it was identified on 6% (4/70) of alleles from SLOS patients (Bianconi et al. 2011). The P51S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P51S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, we interpret P51S to be a pathogenic variant.
Counsyl RCV000178160 SCV000792783 pathogenic Smith-Lemli-Opitz syndrome 2017-07-13 criteria provided, single submitter clinical testing
Invitae RCV000178160 SCV000959206 pathogenic Smith-Lemli-Opitz syndrome 2018-08-09 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 51 of the DHCR7 protein (p.Pro51Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from another pathogenic variant in individuals affected with Smith- Lemli-Opitz syndrome  (PMID: 16181459,9653161). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 93712). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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