NM_001360.3(DHCR7):c.1325A>G (p.His442Arg) AND Smith-Lemli-Opitz syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 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:: RCV001059047.9

Allele description [Variation Report for NM_001360.3(DHCR7):c.1325A>G (p.His442Arg)]

NM_001360.3(DHCR7):c.1325A>G (p.His442Arg)

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.1325A>G (p.His442Arg)

HGVS:

NC_000011.10:g.71435478T>C
NG_012655.2:g.17954A>G
NM_001163817.2:c.1325A>G
NM_001360.3:c.1325A>GMANE SELECT
NP_001157289.1:p.His442Arg
NP_001351.2:p.His442Arg
LRG_340t1:c.1325A>G
LRG_340:g.17954A>G
NC_000011.9:g.71146524T>C
NM_001360.2:c.1325A>G

Protein change:

H442R

Links:

dbSNP: rs1949265616

NCBI 1000 Genomes Browser:

rs1949265616

Molecular consequence:

NM_001163817.2:c.1325A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001360.3:c.1325A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001223651	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28503313, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001223651

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel DHCR7 mutation in a case of Smith-Lemli-Opitz syndrome showing 46,XY disorder of sex development.

Tamura M, Isojima T, Kasama T, Mafune R, Shimoda K, Yasudo H, Tanaka H, Takahashi C, Oka A, Kitanaka S.

Hum Genome Var. 2017;4:17015. doi: 10.1038/hgv.2017.15.

PubMed [citation]

PMID:: 28503313
PMCID:: PMC5425407

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001223651.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 442 of the DHCR7 protein (p.His442Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Smith‚ÄìLemli‚ÄìOpitz syndrome (PMID: 28503313; Invitae). 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: 854086). 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. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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