NM_005199.5(CHRNG):c.397del (p.Ser133fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 28, 2023
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:: RCV000497452.9

Allele description

NM_005199.5(CHRNG):c.397del (p.Ser133fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_005199.5(CHRNG):c.397del (p.Ser133fs)

HGVS:

NC_000002.12:g.232541420del
NG_012954.2:g.6729del
NM_005199.5:c.397delMANE SELECT
NP_005190.4:p.Ser133fs
LRG_1275t1:c.397del
LRG_1275:g.6729del
LRG_1275p1:p.Ser133fs
NC_000002.11:g.233406130del
NC_000002.11:g.233406130delT
NG_012954.1:g.6694del
NM_005199.4:c.397del
NM_005199.4:c.397delT

Protein change:

S133fs

Links:

dbSNP: rs780249576

NCBI 1000 Genomes Browser:

rs780249576

Molecular consequence:

NM_005199.5:c.397del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000589554	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 25, 2019)	germline	clinical testing	Citation Link,
SCV001588426	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16826520, 22167768, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000589554

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Nov 25, 2019)

germline

clinical testing

Citation Link,

SCV001588426

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

CHRNG genotype-phenotype correlations in the multiple pterygium syndromes.

Vogt J, Morgan NV, Rehal P, Faivre L, Brueton LA, Becker K, Fryns JP, Holder S, Islam L, Kivuva E, Lynch SA, Touraine R, Wilson LC, MacDonald F, Maher ER.

J Med Genet. 2012 Jan;49(1):21-6. doi: 10.1136/jmedgenet-2011-100378.

PubMed [citation]

PMID:: 22167768

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000589554.5

#	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; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22167768)

#	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 Invitae, SCV001588426.4

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

Description

This sequence change creates a premature translational stop signal (p.Ser133Profs*50) 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 (rs780249576, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with Escobar variant multiple pterygium syndrome (PMID: 22167768). ClinVar contains an entry for this variant (Variation ID: 431955). 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

Last Updated: Feb 28, 2024

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