NM_001360.3(DHCR7):c.1139G>A (p.Cys380Tyr) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 2016
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:: RCV002453569.3

Allele description [Variation Report for NM_001360.3(DHCR7):c.1139G>A (p.Cys380Tyr)]

NM_001360.3(DHCR7):c.1139G>A (p.Cys380Tyr)

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.1139G>A (p.Cys380Tyr)

HGVS:

NC_000011.10:g.71435664C>T
NG_012655.2:g.17768G>A
NM_001163817.2:c.1139G>A
NM_001360.3:c.1139G>AMANE SELECT
NP_001157289.1:p.Cys380Tyr
NP_001351.2:p.Cys380Tyr
NP_001351.2:p.Cys380Tyr
LRG_340t1:c.1139G>A
LRG_340:g.17768G>A
LRG_340p1:p.Cys380Tyr
NC_000011.9:g.71146710C>T
NM_001360.2:c.1139G>A
Q9UBM7:p.Cys380Tyr
c.1139G>A (p.Cys380Tyr)

Protein change:

C380Y

Links:

UniProtKB: Q9UBM7#VAR_023175; dbSNP: rs779709646

NCBI 1000 Genomes Browser:

rs779709646

Molecular consequence:

NM_001163817.2:c.1139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001360.3:c.1139G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002612936	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 3, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10677299, 16983147, 17974928, 25405082 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002612936

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 3, 2016)

germline

clinical testing

PubMed (4)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Increased nonsterol isoprenoids, dolichol and ubiquinone, in the Smith-Lemli-Opitz syndrome: effects of dietary cholesterol.

Pappu AS, Connor WE, Merkens LS, Jordan JM, Penfield JA, Illingworth DR, Steiner RD.

J Lipid Res. 2006 Dec;47(12):2789-98. Epub 2006 Sep 18.

PubMed [citation]

PMID:: 16983147

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002612936.2

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

Description

The p.C380Y pathogenic mutation (also known as c.1139G>A), located in coding exon 7 of the DHCR7 gene, results from a G to A substitution at nucleotide position 1139. The cysteine at codon 380 is replaced by tyrosine, an amino acid with highly dissimilar properties. This mutation has been observed in homozygous and heterozygous states in multiple individuals with clinical and biochemical features characteristic of Smith-Lemli-Optiz syndrome (SLOS) (Witsch-Baumgartner M, et al. Am. J. Hum. Genet. 2000; 66(2):402-12, Pappu AS, et al. J. Lipid Res. 2006; 47(12):2789-98, Bukelis I, et al. Am J Psychiatry 2007; 164(11):1655-61). In one study using an immunoreactivity assay, protein expression of this alteration was observed to be 40% of wild type levels (Witsch-Baumgartner M, et al. Am. J. Hum. Genet. 2000; 66(2):402-12). In addition, a different mutation located at the same position, p.C380R, has been detected in individuals with SLOS, and was shown to decrease protein expression to 5% of wild type levels (Witsch-Baumgartner M, et al. Am. J. Hum. Genet. 2000; 66(2):402-12, Nowaczyk MJ, et al. Am. J. Med. Genet. 2001; 103(3):223-5). Based on the supporting evidence, p.C380Y 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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