ClinVar Genomic variation as it relates to human health
NM_005199.5(CHRNG):c.256C>T (p.Arg86Cys)
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
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NM_005199.5(CHRNG):c.256C>T (p.Arg86Cys)
Variation ID: 397615 Accession: VCV000397615.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q37.1 2: 232540617 (GRCh38) [ NCBI UCSC ] 2: 233405327 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 27, 2017 Apr 15, 2024 Mar 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005199.5:c.256C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005190.4:p.Arg86Cys missense NC_000002.12:g.232540617C>T NC_000002.11:g.233405327C>T NG_012954.2:g.5926C>T LRG_1275:g.5926C>T LRG_1275t1:c.256C>T LRG_1275p1:p.Arg86Cys - Protein change
- R86C
- Other names
- p.(Arg86Cys)
- Canonical SPDI
- NC_000002.12:232540616:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00004
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 | ||
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HI score
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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. |
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CHRNG | - | - |
GRCh38 GRCh37 |
332 | 528 |
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. |
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Likely pathogenic (1) |
criteria provided, single submitter
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Aug 22, 2016 | RCV000449634.2 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 29, 2024 | RCV001007785.6 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 8, 2023 | RCV000762330.20 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 14, 2023 | RCV003479120.1 |
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. |
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Likely pathogenic
(Aug 22, 2016)
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criteria provided, single submitter
Method: clinical testing
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Peripheral neuropathy
Affected status: yes
Allele origin:
germline
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Claritas Genomics
Accession: SCV000537827.1
First in ClinVar: Mar 27, 2017 Last updated: Mar 27, 2017 |
Sex: female
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Likely pathogenic
(Dec 19, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449542.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 3
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Pathogenic
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003837510.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16826520, 31230720, 30868735, 34426522, 26752647) (less)
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Likely pathogenic
(Apr 20, 2023)
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criteria provided, single submitter
Method: research
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Autosomal recessive multiple pterygium syndrome
Affected status: yes
Allele origin:
maternal
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Duke University Health System Sequencing Clinic, Duke University Health System
Accession: SCV003918956.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
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Likely pathogenic
(Jan 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive multiple pterygium syndrome
Affected status: yes
Allele origin:
inherited
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Center of Genomic medicine, Geneva, University Hospital of Geneva
Accession: SCV004098980.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The patient harbours this variant in an homozygous state, each copy being inherited form each parent
Number of individuals with the variant: 3
Age: 20-29 years
Sex: female
Ethnicity/Population group: Kurdish
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Pathogenic
(Nov 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lethal multiple pterygium syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004223810.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
Variant summary: CHRNG c.256C>T (p.Arg86Cys) results in a non-conservative amino acid change located in the neurotransmitter-gated ion-channel transmembrane domain (IPR006029) of the encoded protein sequence. … (more)
Variant summary: CHRNG c.256C>T (p.Arg86Cys) results in a non-conservative amino acid change located in the neurotransmitter-gated ion-channel transmembrane domain (IPR006029) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248786 control chromosomes (gnomAD). c.256C>T has been reported in the literature as a biallelic genotype in multiple individuals affected with Escobar Syndrome/Lethal Multiple Pterygium Syndrome - CHRNG Related (e.g. Hoffmann_2006, Bayram_2016, Pehlivan_2019). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 16826520, 26752647, 31230720). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Mar 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive multiple pterygium syndrome
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004807824.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Aug 01, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000892636.20
First in ClinVar: Mar 31, 2019 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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Autosomal recessive multiple pterygium syndrome
This variant was identified in an
(more...)
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Accession: SCV001167470.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Number of individuals with the variant: 11
Family history: yes
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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 |
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The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance. | Pehlivan D | American journal of human genetics | 2019 | PMID: 31230720 |
Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin. | Bayram Y | The Journal of clinical investigation | 2016 | PMID: 26752647 |
Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. | Hoffmann K | American journal of human genetics | 2006 | PMID: 16826520 |
Text-mined citations for rs777219451 ...
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.