NM_001360.3(DHCR7):c.1012del (p.Val338fs) AND Smith-Lemli-Opitz syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 9, 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:: RCV003033989.2

Allele description [Variation Report for NM_001360.3(DHCR7):c.1012del (p.Val338fs)]

NM_001360.3(DHCR7):c.1012del (p.Val338fs)

Gene:

DHCR7:7-dehydrocholesterol reductase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q13.4

Genomic location:

Preferred name:

NM_001360.3(DHCR7):c.1012del (p.Val338fs)

HGVS:

NC_000011.10:g.71435791del
NG_012655.2:g.17641del
NM_001163817.2:c.1012del
NM_001360.3:c.1012delMANE SELECT
NP_001157289.1:p.Val338fs
NP_001351.2:p.Val338Trpfs
NP_001351.2:p.Val338fs
LRG_340t1:c.1012del
LRG_340:g.17641del
LRG_340p1:p.Val338Trpfs
NC_000011.9:g.71146837del
NM_001360.2:c.1012delG

Protein change:

V338fs

Molecular consequence:

NM_001163817.2:c.1012del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001360.3:c.1012del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003323917	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 9, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21990131, 22391996, 23042628, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003323917

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 9, 2022)

germline

clinical testing

PubMed (4)
[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

Adrenal function in Smith-Lemli-Opitz syndrome.

Bianconi SE, Conley SK, Keil MF, Sinaii N, Rother KI, Porter FD, Stratakis CA.

Am J Med Genet A. 2011 Nov;155A(11):2732-8. doi: 10.1002/ajmg.a.34271. Epub 2011 Oct 11.

PubMed [citation]

PMID:: 21990131
PMCID:: PMC3488380

No evidence for mevalonate shunting in moderately affected children with Smith-Lemli-Opitz syndrome.

Roullet JB, Merkens LS, Pappu AS, Jacobs MD, Winter R, Connor WE, Steiner RD.

J Inherit Metab Dis. 2012 Sep;35(5):859-69. doi: 10.1007/s10545-012-9453-6. Epub 2012 Mar 6.

PubMed [citation]

PMID:: 22391996
PMCID:: PMC3404269

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003323917.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant disrupts a region of the DHCR7 protein in which other variant(s) (p.Val466Met) have been determined to be pathogenic (PMID: 21990131, 22391996, 23042628; Invitae). 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. This variant has not been reported in the literature in individuals affected with DHCR7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val338Trpfs*75) in the DHCR7 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 138 amino acid(s) of the DHCR7 protein.

#	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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