NM_000349.3(STAR):c.545G>A (p.Arg182His) AND Congenital lipoid adrenal hyperplasia due to STAR deficency

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Feb 9, 2021
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:: RCV000009558.8

Allele description [Variation Report for NM_000349.3(STAR):c.545G>A (p.Arg182His)]

NM_000349.3(STAR):c.545G>A (p.Arg182His)

Gene:

STAR:steroidogenic acute regulatory protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p11.23

Genomic location:

Preferred name:

NM_000349.3(STAR):c.545G>A (p.Arg182His)

HGVS:

NC_000008.11:g.38146068C>T
NG_011827.1:g.10015G>A
NM_000349.3:c.545G>AMANE SELECT
NP_000340.2:p.Arg182His
NC_000008.10:g.38003586C>T
NM_000349.2:c.545G>A
p.ARG182HIS

Protein change:

R182H; ARG182HIS

Links:

OMIM: 600617.0010; dbSNP: rs104894086

NCBI 1000 Genomes Browser:

rs104894086

Molecular consequence:

NM_000349.3:c.545G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital lipoid adrenal hyperplasia due to STAR deficency
Synonyms:: ADRENAL HYPERPLASIA I; Congenital lipoid adrenal hyperplasia; Lipoid CAH; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008725; MedGen: C0342474; Orphanet: 418; OMIM: 201710

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029776	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2005)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 15546900, 11509019
SCV000797248	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Jan 18, 2018)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17301050, 26523528, 15546900 Citation Link,
SCV001460463	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV002021970	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 9, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Molecular and structural analysis of two novel StAR mutations in patients with lipoid congenital adrenal hyperplasia.

Achermann JC, Meeks JJ, Jeffs B, Das U, Clayton PE, Brook CG, Jameson JL.

Mol Genet Metab. 2001 Aug;73(4):354-7.

PubMed [citation]

PMID:: 11509019

Cholesterol binding does not predict activity of the steroidogenic acute regulatory protein, StAR.

Baker BY, Epand RF, Epand RM, Miller WL.

J Biol Chem. 2007 Apr 6;282(14):10223-32. Epub 2007 Feb 13.

PubMed [citation]

PMID:: 17301050

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000029776.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Among 8 patients with congenital lipoid adrenal hyperplasia (201710) from 6 apparently unrelated Saudi Arabian families, Chen et al. (2005) reported that 7 were homozygous for an arg182-to-his (R182H) mutation in the steroidogenic acute regulatory protein (STAR). Onset of symptoms ranged from 1 month to 14 months. The R182H mutation was recreated in a human STAR cDNA expression vector and found to be wholly inactive in a standard assay of COS-1 cells cotransfected with the cholesterol side-chain cleavage enzyme system. Thus, the loss of all assayable activity in vitro correlated poorly with the later onset of clinical symptoms in these patients. Chen et al. (2005) concluded that lipoid CAH may present much later in life than previously thought.

Achermann et al. (2001) described this mutation in a patient from Qatar with onset of clinical symptoms and laboratory evidence of salt loss noted at 3 weeks of age.

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

From Counsyl, SCV000797248.1

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

#	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 Natera, Inc., SCV001460463.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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 Revvity Omics, Revvity, SCV002021970.3

#	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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