NM_005199.5(CHRNG):c.459dup (p.Val154fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 31, 2024
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:: RCV000522117.15

Allele description [Variation Report for NM_005199.5(CHRNG):c.459dup (p.Val154fs)]

NM_005199.5(CHRNG):c.459dup (p.Val154fs)

Gene:

CHRNG:cholinergic receptor nicotinic gamma subunit [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_005199.5(CHRNG):c.459dup (p.Val154fs)

HGVS:

NC_000002.12:g.232541482dup
NG_012954.2:g.6791dup
NM_005199.5:c.459dupMANE SELECT
NP_005190.4:p.Val154fs
LRG_1275t1:c.459dup
LRG_1275:g.6791dup
LRG_1275p1:p.Val154fs
NC_000002.11:g.233406191_233406192insA
NC_000002.11:g.233406192dup
NG_012954.1:g.6756dup
NM_005199.4:c.459dup
NM_005199.4:c.459dupA
NM_005199.5:c.459dupAMANE SELECT

Protein change:

V154fs

Links:

OMIM: 100730.0008; dbSNP: rs774279192

NCBI 1000 Genomes Browser:

rs774279192

Molecular consequence:

NM_005199.5:c.459dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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gamma-aminobutyric acid receptor-associated protein [Danio rerio]
gamma-aminobutyric acid receptor-associated protein [Danio rerio]
gi|1896066483|ref|NP_001373316.1|

Protein
Brugmansia suaveolens APETALA2 mRNA, partial cds
Brugmansia suaveolens APETALA2 mRNA, partial cds
gi|1983932013|gb|MW375894.1|

Nucleotide
nad2 [Clathrina clathrus]
nad2 [Clathrina clathrus]
Gene ID:15332555

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000617355	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 1, 2022)	germline	clinical testing	Citation Link,
SCV001414922	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16826520, 16826531, 22167768, 24038971, 24254455, 28492532
SCV002019316	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 12, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000617355

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 1, 2022)

germline

clinical testing

Citation Link,

SCV001414922

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV002019316

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 12, 2019)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit.

Hoffmann K, Muller JS, Stricker S, Megarbane A, Rajab A, Lindner TH, Cohen M, Chouery E, Adaimy L, Ghanem I, Delague V, Boltshauser E, Talim B, Horvath R, Robinson PN, Lochmüller H, Hübner C, Mundlos S.

Am J Hum Genet. 2006 Aug;79(2):303-12. Epub 2006 Jun 20.

PubMed [citation]

PMID:: 16826520
PMCID:: PMC1559482

Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome.

Morgan NV, Brueton LA, Cox P, Greally MT, Tolmie J, Pasha S, Aligianis IA, van Bokhoven H, Marton T, Al-Gazali L, Morton JE, Oley C, Johnson CA, Trembath RC, Brunner HG, Maher ER.

Am J Hum Genet. 2006 Aug;79(2):390-5. Epub 2006 Jun 20.

PubMed [citation]

PMID:: 16826531
PMCID:: PMC1559492

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000617355.4

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24254455, 29054425, 34440395, 33060286, 30266093, 34411415, 32403337, 31980526, 24038971, 16826531, 30868735, 22167768, 25957469, 22482962, 32536119, 34426522, 31589614)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001414922.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Val154Serfs*24) in the CHRNG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHRNG are known to be pathogenic (PMID: 16826520). This variant is present in population databases (rs774279192, gnomAD 0.06%). This premature translational stop signal has been observed in individuals with multiple pterygium syndrome (PMID: 16826531, 22167768, 24038971, 24254455). ClinVar contains an entry for this variant (Variation ID: 449338). For these reasons, this variant has been classified as Pathogenic.

#	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, SCV002019316.3

#	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: Oct 26, 2024

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