NM_005199.5(CHRNG):c.401_402del (p.Pro134fs) AND Autosomal recessive multiple pterygium syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 15, 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:: RCV000498334.8

Allele description [Variation Report for NM_005199.5(CHRNG):c.401_402del (p.Pro134fs)]

NM_005199.5(CHRNG):c.401_402del (p.Pro134fs)

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.401_402del (p.Pro134fs)

HGVS:

NC_000002.12:g.232541424_232541425del
NG_012954.2:g.6733_6734del
NM_005199.5:c.401_402delMANE SELECT
NP_005190.4:p.Pro134fs
LRG_1275t1:c.401_402del
LRG_1275:g.6733_6734del
LRG_1275p1:p.Pro134fs
NC_000002.11:g.233406134_233406135del
NG_012954.1:g.6698_6699del
NM_005199.4:c.401_402del
NM_005199.4:c.401_402delCT
p.Pro134Argfs*43

Protein change:

P134fs

Links:

dbSNP: rs747067203

NCBI 1000 Genomes Browser:

rs747067203

Molecular consequence:

NM_005199.5:c.401_402del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Autosomal recessive multiple pterygium syndrome
Synonyms:: MULTIPLE PTERYGIUM SYNDROME, ESCOBAR VARIANT; Multiple pterygium syndrome Escobar type; Multiple pterygium syndrome nonlethal type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009926; MedGen: C0265261; Orphanet: 2990; OMIM: 265000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000590869	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 4, 2016)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000807223	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 15, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 25326635
SCV000996182	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 9, 2018)	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

SCV000590869

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 4, 2016)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000807223

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 15, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000996182

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 9, 2018)

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	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular findings among patients referred for clinical whole-exome sequencing.

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, et al.

JAMA. 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601.

PubMed [citation]

PMID:: 25326635
PMCID:: PMC4326249

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV000590869.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	unknown	yes	1	not provided	not provided		1	not provided	not provided	See 1

Co-occurrences

#	Zygosity	Alleles	Number of Observations
1		NM_005199.4:c.250G>A

From Baylor Genetics, SCV000807223.3

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

#	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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV000996182.1

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

Description

This frameshifting variant in exon 5 of 12 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a homozygous change in patients with Escobar Variant Multiple Pterygium Syndrome (EVMPS) (PMID: 16826531, 27245440). This alteration is present in the gnomAD population database at a frequency of 0.0079% (22/277144) and thus is presumed to be rare. Based on the available evidence, the c.401_402delCT (p.Pro134ArgfsTer43) variant is classified as pathogenic.

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

Last Updated: Sep 29, 2024

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