NM_001360.3(DHCR7):c.808A>G (p.Met270Val) AND Smith-Lemli-Opitz syndrome

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Oct 3, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000672300.8

Allele description [Variation Report for NM_001360.3(DHCR7):c.808A>G (p.Met270Val)]

NM_001360.3(DHCR7):c.808A>G (p.Met270Val)

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.808A>G (p.Met270Val)

HGVS:

NC_000011.10:g.71438902T>C
NG_012655.2:g.14530A>G
NM_001163817.2:c.808A>G
NM_001360.3:c.808A>GMANE SELECT
NP_001157289.1:p.Met270Val
NP_001351.2:p.Met270Val
NP_001351.2:p.Met270Val
LRG_340t1:c.808A>G
LRG_340:g.14530A>G
LRG_340p1:p.Met270Val
NC_000011.9:g.71149948T>C
NM_001360.2:c.808A>G

Protein change:

M270V

Links:

dbSNP: rs1555146021

NCBI 1000 Genomes Browser:

rs1555146021

Molecular consequence:

NM_001163817.2:c.808A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001360.3:c.808A>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; RSH SYNDROME; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010035; MedGen: C0175694; Orphanet: 818; OMIM: 270400

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002244278	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 12, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18249054, 28492532
SCV004183559	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 3, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002244278

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 12, 2023)

germline

clinical testing

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

SCV004183559

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 3, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

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

Mutations in the human DHCR7 gene.

Witsch-Baumgartner M, Löffler J, Utermann G.

Hum Mutat. 2001 Mar;17(3):172-82.

PubMed [citation]

PMID:: 11241839

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000797396.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002244278.4

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

Description

For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 556307). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 18249054). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 270 of the DHCR7 protein (p.Met270Val).

#	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

From Baylor Genetics, SCV004183559.1

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

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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000797396	Counsyl	flagged submission Reason: Claim with insufficient supporting evidence Notes: None (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jan 24, 2018)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15521979, 11241839 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000797396

Counsyl

flagged submission

Reason: Claim with insufficient supporting evidence

Notes: None

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Jan 24, 2018)

unknown

clinical testing

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

Citation Link

Last Updated: Apr 7, 2025

ClinVar

Relating variation to medicine