ClinVar Genomic variation as it relates to human health
NM_000349.3(STAR):c.544C>T (p.Arg182Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000349.3(STAR):c.544C>T (p.Arg182Cys)
Variation ID: 550550 Accession: VCV000550550.12
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 8p11.23 8: 38146069 (GRCh38) [ NCBI UCSC ] 8: 38003587 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 5, 2018 Apr 15, 2024 Apr 4, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000349.3:c.544C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000340.2:p.Arg182Cys missense NC_000008.11:g.38146069G>A NC_000008.10:g.38003587G>A NG_011827.1:g.10014C>T - Protein change
- R182C
- Other names
- -
- Canonical SPDI
- NC_000008.11:38146068:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
STAR | - | - |
GRCh38 GRCh37 |
361 | 443 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Apr 4, 2024 | RCV000665326.6 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 19, 2023 | RCV001211857.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely pathogenic
(Jan 31, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital lipoid adrenal hyperplasia due to STAR deficency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000789427.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
|
|
Pathogenic
(May 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital lipoid adrenal hyperplasia due to STAR deficency
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002521179.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). In silico tool predictions suggest damaging effect … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.91; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000550550). A different missense change at the same codon (p.Arg182His) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000008995). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hyponatremia (present) , Hyperkalemia (present) , Dehydration (present) , Hyperpigmentation of the skin (present) , Adrenal insufficiency (present) , Increased circulating ACTH level (present) , … (more)
Hyponatremia (present) , Hyperkalemia (present) , Dehydration (present) , Hyperpigmentation of the skin (present) , Adrenal insufficiency (present) , Increased circulating ACTH level (present) , Decreased circulating cortisol level (present) (less)
|
|
Pathogenic
(Aug 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital lipoid adrenal hyperplasia due to STAR deficency
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002802670.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(May 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001383419.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg182 amino acid residue in STAR. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg182 amino acid residue in STAR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11509019, 15546900). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STAR protein function. ClinVar contains an entry for this variant (Variation ID: 550550). This missense change has been observed in individual(s) with lipoid adrenal hyperplasia (PMID: 16118340, 24790358, 24904850). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs369232492, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 182 of the STAR protein (p.Arg182Cys). (less)
|
|
Pathogenic
(Apr 04, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital lipoid adrenal hyperplasia due to STAR deficency
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004809922.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
|
|
Pathogenic
(Feb 03, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Congenital lipoid adrenal hyperplasia
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002083262.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Phenotypic variability in congenital lipoid adrenal hyperplasia. | Joshi R | Indian pediatrics | 2014 | PMID: 24953586 |
p.R182C mutation in Korean twin with congenital lipoid adrenal hyperplasia. | Park HW | Annals of pediatric endocrinology & metabolism | 2013 | PMID: 24904850 |
A Novel Mutation of the Steroidogenic Acute Regulatory Protein (StAR) Gene in a Japanese Patient with Congenital Lipoid Adrenal Hyperplasia. | Ishizu K | Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology | 2008 | PMID: 24790358 |
Phenotypic features associated with mutations in steroidogenic acute regulatory protein. | Bhangoo A | The Journal of clinical endocrinology and metabolism | 2005 | PMID: 16118340 |
A genetic isolate of congenital lipoid adrenal hyperplasia with atypical clinical findings. | Chen X | The Journal of clinical endocrinology and metabolism | 2005 | PMID: 15546900 |
Molecular and structural analysis of two novel StAR mutations in patients with lipoid congenital adrenal hyperplasia. | Achermann JC | Molecular genetics and metabolism | 2001 | PMID: 11509019 |
Text-mined citations for rs369232492 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.