NM_001360.3(DHCR7):c.546G>A (p.Trp182Ter) AND Smith-Lemli-Opitz syndrome

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Oct 4, 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:: RCV000761593.12

Allele description [Variation Report for NM_001360.3(DHCR7):c.546G>A (p.Trp182Ter)]

NM_001360.3(DHCR7):c.546G>A (p.Trp182Ter)

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.546G>A (p.Trp182Ter)

HGVS:

NC_000011.10:g.71441307C>T
NG_012655.2:g.12125G>A
NM_001163817.2:c.546G>A
NM_001360.3:c.546G>AMANE SELECT
NP_001157289.1:p.Trp182Ter
NP_001351.2:p.Trp182Ter
NP_001351.2:p.Trp182Ter
LRG_340t1:c.546G>A
LRG_340:g.12125G>A
LRG_340p1:p.Trp182Ter
NC_000011.9:g.71152353C>T
NM_001360.2:c.546G>A

Protein change:

W182*

Links:

dbSNP: rs1032242817

NCBI 1000 Genomes Browser:

rs1032242817

Molecular consequence:

NM_001163817.2:c.546G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001360.3:c.546G>A - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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Homo sapiens secretin (SCT), mRNA
Homo sapiens secretin (SCT), mRNA
gi|11345449|ref|NM_021920.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000891753	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-SouthSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 22, 2018)	maternal	research	PubMed (1) [See all records that cite this PMID]
SCV001163332	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001381435	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9634533, 10677299, 28492532
SCV002810553	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 9, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003827559	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 12, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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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
not provided	maternal	yes	1	not provided	not provided	1	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome.

Wassif CA, Maslen C, Kachilele-Linjewile S, Lin D, Linck LM, Connor WE, Steiner RD, Porter FD.

Am J Hum Genet. 1998 Jul;63(1):55-62.

PubMed [citation]

PMID:: 9634533
PMCID:: PMC1377256

Mutational spectrum in the Delta7-sterol reductase gene and genotype-phenotype correlation in 84 patients with Smith-Lemli-Opitz syndrome.

Witsch-Baumgartner M, Fitzky BU, Ogorelkova M, Kraft HG, Moebius FF, Glossmann H, Seedorf U, Gillessen-Kaesbach G, Hoffmann GF, Clayton P, Kelley RI, Utermann G.

Am J Hum Genet. 2000 Feb;66(2):402-12.

PubMed [citation]

PMID:: 10677299
PMCID:: PMC1288092

See all PubMed Citations (4)

Details of each submission

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-SouthSeq, SCV000891753.1

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

Description

ACMG codes: PVS1, PM2, PM3

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

From Baylor Genetics, SCV001163332.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001381435.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Trp182*) in the DHCR7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DHCR7 are known to be pathogenic (PMID: 9634533, 10677299). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DHCR7-related conditions. ClinVar contains an entry for this variant (Variation ID: 623647). 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

From Fulgent Genetics, Fulgent Genetics, SCV002810553.1

#	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

From Revvity Omics, Revvity, SCV003827559.2

#	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	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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