NM_001360.3(DHCR7):c.1349_1350delinsTG (p.Arg450Leu) AND Inborn genetic diseases

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 28, 2020
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:: RCV002381791.1

Allele description

NM_001360.3(DHCR7):c.1349_1350delinsTG (p.Arg450Leu)

Gene:

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

Variant type:

Indel

Cytogenetic location:

11q13.4

Genomic location:

Preferred name:

NM_001360.3(DHCR7):c.1349_1350delinsTG (p.Arg450Leu)

HGVS:

NC_000011.10:g.71435453_71435454delinsCA
NG_012655.2:g.17978_17979delinsTG
NM_001163817.2:c.1349_1350delinsTG
NM_001360.3:c.1349_1350delinsTGMANE SELECT
NP_001157289.1:p.Arg450Leu
NP_001351.2:p.Arg450Leu
NP_001351.2:p.Arg450Leu
LRG_340t1:c.1349_1350delinsTG
LRG_340:g.17978_17979delinsTG
LRG_340p1:p.Arg450Leu
NC_000011.9:g.71146499_71146500delinsCA
NM_001360.2:c.1349_1350delGCinsTG
NM_001360.2:c.1349_1350delinsTG

Protein change:

R450L

Links:

dbSNP: rs1591107040

NCBI 1000 Genomes Browser:

rs1591107040

Molecular consequence:

NM_001163817.2:c.1349_1350delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001360.3:c.1349_1350delinsTG - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002690293	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Jul 28, 2020)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 10405455, 10677299, 11241839, 15670717, 15805162, 15896653, 16181459, 21990131, 22391996, 23042628, 25405082, 27513191, 28349652 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002690293

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Jul 28, 2020)

germline

clinical testing

PubMed (13)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Biochemical variants of Smith-Lemli-Opitz syndrome.

Neklason DW, Andrews KM, Kelley RI, Metherall JE.

Am J Med Genet. 1999 Aug 27;85(5):517-23.

PubMed [citation]

PMID:: 10405455

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 (13)

Details of each submission

From Ambry Genetics, SCV002690293.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (13)

Description

The c.1349_1350delGCinsTG pathogenic mutation, located in coding exon 7 of the DHCR7 gene, results from an in-frame deletion of GC and insertion of TG at nucleotide positions 1349 to 1350. This results in the substitution of the arginine residue for a leucine residue at codon 450, an amino acid with dissimilar properties. This alteration has been detected in conjunction with other known pathogenic mutations in DHCR7 (c.964-1G>C, p.R242C, p.Q95*/p.Q98*) in several individuals with Smith-Lemli-Opitz Syndrome (Witsch-Baumgartner M et al. Am. J. Hum. Genet., 2000 Feb;66:402-12; Correa-Cerro LS et al. Mol. Genet. Metab., 2005 Feb;84:112-26; Wassif CA et al. Genet. Med., 2017 03;19:297-305; Chang S et al. Mol Genet Metab Rep, 2014;1:431-442; Anstey AV et al. Br. J. Dermatol., 2005 Oct;153:774-9; Bianconi SE et al. Am. J. Med. Genet. A, 2011 Nov;155A:2732-8; Eroglu Y et al. Am. J. Med. Genet. A, 2017 Aug;173:2097-2100). In addition, several functional studies showed that this alteration resulted in significantly reduced enzymatic activity when expressed in cell lines (Witsch-Baumgartner M et al. Am. J. Hum. Genet., 2000 Feb;66:402-12; Correa-Cerro LS et al. Mol. Genet. Metab., 2005 Feb;84:112-26; Wassif CA et al. Genet. Med., 2017 03;19:297-305). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Apr 15, 2024

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