NM_001360.3(DHCR7):c.1113G>A (p.Trp371Ter) AND Smith-Lemli-Opitz syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 13, 2022
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:: RCV003066242.2

Allele description [Variation Report for NM_001360.3(DHCR7):c.1113G>A (p.Trp371Ter)]

NM_001360.3(DHCR7):c.1113G>A (p.Trp371Ter)

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.1113G>A (p.Trp371Ter)

HGVS:

NC_000011.10:g.71435690C>T
NG_012655.2:g.17742G>A
NM_001163817.2:c.1113G>A
NM_001360.3:c.1113G>AMANE SELECT
NP_001157289.1:p.Trp371Ter
NP_001351.2:p.Trp371Ter
NP_001351.2:p.Trp371Ter
LRG_340t1:c.1113G>A
LRG_340:g.17742G>A
LRG_340p1:p.Trp371Ter
NC_000011.9:g.71146736C>T
NM_001360.2:c.1113G>A

Protein change:

W371*

Molecular consequence:

NM_001163817.2:c.1113G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001360.3:c.1113G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003353082	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15776424, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003353082

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 13, 2022)

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

Identification of 14 novel mutations in DHCR7 causing the Smith-Lemli-Opitz syndrome and delineation of the DHCR7 mutational spectra in Spain and Italy.

Witsch-Baumgartner M, Clayton P, Clusellas N, Haas D, Kelley RI, Krajewska-Walasek M, Lechner S, Rossi M, Zschocke J, Utermann G.

Hum Mutat. 2005 Apr;25(4):412.

PubMed [citation]

PMID:: 15776424

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 Invitae, SCV003353082.2

#	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 creates a premature translational stop signal (p.Trp371*) in the DHCR7 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 105 amino acid(s) of the DHCR7 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). A different variant (c.1112G>A) giving rise to the same protein effect has been determined to be pathogenic (Invitae). This suggests that this variant is also likely to be causative of disease. This variant disrupts a region of the DHCR7 protein in which other variant(s) (p.Phe475Ser) have been determined to be pathogenic (PMID: 15776424). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Feb 20, 2024

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