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NM_001360.3(DHCR7):c.925G>A (p.Gly309Ser) AND Smith-Lemli-Opitz syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 27, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001972753.5

Allele description [Variation Report for NM_001360.3(DHCR7):c.925G>A (p.Gly309Ser)]

NM_001360.3(DHCR7):c.925G>A (p.Gly309Ser)

Gene:
DHCR7:7-dehydrocholesterol reductase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.4
Genomic location:
Preferred name:
NM_001360.3(DHCR7):c.925G>A (p.Gly309Ser)
HGVS:
  • NC_000011.10:g.71437850C>T
  • NG_012655.2:g.15582G>A
  • NM_001163817.2:c.925G>A
  • NM_001360.3:c.925G>AMANE SELECT
  • NP_001157289.1:p.Gly309Ser
  • NP_001351.2:p.Gly309Ser
  • LRG_340:g.15582G>A
  • NC_000011.9:g.71148896C>T
Protein change:
G309S
Links:
dbSNP: rs2135941811
NCBI 1000 Genomes Browser:
rs2135941811
Molecular consequence:
  • NM_001163817.2:c.925G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001360.3:c.925G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Smith-Lemli-Opitz syndrome (SLOS)
Synonyms:
LETHAL ACRODYSGENITAL SYNDROME; POLYDACTYLY, SEX REVERSAL, RENAL HYPOPLASIA, AND UNILOBAR LUNG; RUTLEDGE LETHAL MULTIPLE CONGENITAL ANOMALY SYNDROME; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010035; MedGen: C0175694; Orphanet: 818; OMIM: 270400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002245655Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 27, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations.

Witsch-Baumgartner M, Ciara E, Löffler J, Menzel HJ, Seedorf U, Burn J, Gillessen-Kaesbach G, Hoffmann GF, Fitzky BU, Mundy H, Clayton P, Kelley RI, Krajewska-Walasek M, Utermann G.

Eur J Hum Genet. 2001 Jan;9(1):45-50.

PubMed [citation]
PMID:
11175299

DHCR7 mutations and genotype-phenotype correlation in 37 Polish patients with Smith-Lemli-Opitz syndrome.

Ciara E, Nowaczyk MJ, Witsch-Baumgartner M, Malunowicz E, Popowska E, Jezela-Stanek A, Piotrowicz M, Waye JS, Utermann G, Krajewska-Walasek M.

Clin Genet. 2004 Dec;66(6):517-24.

PubMed [citation]
PMID:
15521979
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002245655.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 309 of the DHCR7 protein (p.Gly309Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Smith–Lemli–Opitz syndrome (PMID: 11175299, 15521979, 15805162). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1457935). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024