ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.1342G>A (p.Glu448Lys) (rs80338864)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790762 SCV000233038 pathogenic not provided 2013-08-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000020435 SCV000697853 pathogenic Smith-Lemli-Opitz syndrome 2017-06-30 criteria provided, single submitter clinical testing Variant summary: The DHCR7 c.1342G>A (p.Glu448Lys) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 1/117588 control chromosomes at a frequency of 0.0000085, which does not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301). The variant has been reported in numerous SLOS patients both in the homozygous and compound heterozygous state, and is known as a common disease variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV000020435 SCV001163679 pathogenic Smith-Lemli-Opitz syndrome criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000020435 SCV001193970 likely pathogenic Smith-Lemli-Opitz syndrome 2019-12-12 criteria provided, single submitter clinical testing NM_001360.2(DHCR7):c.1342G>A(E448K) is classified as likely pathogenic in the context of Smith-Lemli-Opitz syndrome. Sources cited for classification include the following: PMID 16181459, 10995508 and 10814720. Classification of NM_001360.2(DHCR7):c.1342G>A(E448K) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000020435 SCV001229233 pathogenic Smith-Lemli-Opitz syndrome 2019-11-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 448 of the DHCR7 protein (p.Glu448Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs80338864, ExAC 0.002%). This variant has been observed to be homozygous or in combination with another DHCR7 variant in several individuals affected with Smith-Lemli-Opitz syndrome (PMID: 10602371, 10995508, 12949967, 12270273). ClinVar contains an entry for this variant (Variation ID: 6792). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000020435 SCV000027390 pathogenic Smith-Lemli-Opitz syndrome 2003-09-15 no assertion criteria provided literature only
GeneReviews RCV000020435 SCV000040848 pathologic Smith-Lemli-Opitz syndrome 2007-10-24 no assertion criteria provided curation Converted during submission to Pathogenic.

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