NM_198904.4(GABRG2):c.968G>A (p.Arg323Gln) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 12, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002316207.9

Allele description [Variation Report for NM_198904.4(GABRG2):c.968G>A (p.Arg323Gln)]

NM_198904.4(GABRG2):c.968G>A (p.Arg323Gln)

Gene:

GABRG2:gamma-aminobutyric acid type A receptor subunit gamma2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q34

Genomic location:

Preferred name:

NM_198904.4(GABRG2):c.968G>A (p.Arg323Gln)

Other names:

p.R323Q:CGG>CAG

HGVS:

NC_000005.10:g.162149153G>A
NG_009290.1:g.86512G>A
NM_000816.3:c.968G>A
NM_001375339.1:c.959G>A
NM_001375340.1:c.923-2577G>A
NM_001375341.1:c.965G>A
NM_001375342.1:c.965G>A
NM_001375343.1:c.1088G>A
NM_001375344.1:c.1007G>A
NM_001375345.1:c.902G>A
NM_001375346.1:c.902G>A
NM_001375347.1:c.881G>A
NM_001375348.1:c.548G>A
NM_001375349.1:c.683G>A
NM_001375350.1:c.548G>A
NM_198903.2:c.1088G>A
NM_198904.4:c.968G>AMANE SELECT
NP_000807.2:p.Arg323Gln
NP_001362268.1:p.Arg320Gln
NP_001362270.1:p.Arg322Gln
NP_001362271.1:p.Arg322Gln
NP_001362272.1:p.Arg363Gln
NP_001362273.1:p.Arg336Gln
NP_001362274.1:p.Arg301Gln
NP_001362275.1:p.Arg301Gln
NP_001362276.1:p.Arg294Gln
NP_001362277.1:p.Arg183Gln
NP_001362278.1:p.Arg228Gln
NP_001362279.1:p.Arg183Gln
NP_944493.2:p.Arg363Gln
NP_944494.1:p.Arg323Gln
NC_000005.9:g.161576159G>A
NM_198904.4:c.968G>A

Protein change:

R183Q; ARG323GLN

Links:

OMIM: 137164.0006; dbSNP: rs397514737

NCBI 1000 Genomes Browser:

rs397514737

Molecular consequence:

NM_001375340.1:c.923-2577G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000816.3:c.968G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.965G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.965G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.1088G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.902G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.902G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.881G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375348.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.683G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375350.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.1088G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.968G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000851296	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 12, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23708187, 25726841, 25730860 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000851296

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 12, 2016)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, et al.

Nat Genet. 2013 Jul;45(7):825-30. doi: 10.1038/ng.2646. Epub 2013 May 26.

PubMed [citation]

PMID:: 23708187
PMCID:: PMC3704157

Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes.

Reinthaler EM, Dejanovic B, Lal D, Semtner M, Merkler Y, Reinhold A, Pittrich DA, Hotzy C, Feucht M, Steinböck H, Gruber-Sedlmayr U, Ronen GM, Neophytou B, Geldner J, Haberlandt E, Muhle H, Ikram MA, van Duijn CM, Uitterlinden AG, Hofman A, Altmüller J, Kawalia A, et al.

Ann Neurol. 2015 Jun;77(6):972-86. doi: 10.1002/ana.24395. Epub 2015 Mar 28.

PubMed [citation]

PMID:: 25726841

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000851296.4

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

Description

The p.R323Q pathogenic mutation (also known as c.968G>A), located in coding exon 8 of the GABRG2 gene, results from a G to A substitution at nucleotide position 968. The arginine at codon 323 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been determined to be the result of a de novo mutation in two patients with epileptic encephalopathies (Carvill GL et al. Nat. Genet., 2013 Jul;45:825-30; Reinthaler EM et al. Ann. Neurol., 2015 Jun;77:972-86). Electrophysiology functional studies indicate this variant results in altered GABAA-R chloride channel kinetics (Reinthaler EM et al. Ann. Neurol., 2015 Jun;77:972-86). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Nov 30, 2024

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