NM_198904.4(GABRG2):c.1000G>A (p.Ala334Thr) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Jul 26, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000518838.24

Allele description [Variation Report for NM_198904.4(GABRG2):c.1000G>A (p.Ala334Thr)]

NM_198904.4(GABRG2):c.1000G>A (p.Ala334Thr)

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.1000G>A (p.Ala334Thr)

HGVS:

NC_000005.10:g.162149185G>A
NG_009290.1:g.86544G>A
NM_000816.3:c.1000G>A
NM_001375339.1:c.991G>A
NM_001375340.1:c.923-2545G>A
NM_001375341.1:c.997G>A
NM_001375342.1:c.997G>A
NM_001375343.1:c.1120G>A
NM_001375344.1:c.1039G>A
NM_001375345.1:c.934G>A
NM_001375346.1:c.934G>A
NM_001375347.1:c.913G>A
NM_001375348.1:c.580G>A
NM_001375349.1:c.715G>A
NM_001375350.1:c.580G>A
NM_198903.2:c.1120G>A
NM_198904.4:c.1000G>AMANE SELECT
NP_000807.2:p.Ala334Thr
NP_000807.2:p.Ala334Thr
NP_001362268.1:p.Ala331Thr
NP_001362270.1:p.Ala333Thr
NP_001362271.1:p.Ala333Thr
NP_001362272.1:p.Ala374Thr
NP_001362273.1:p.Ala347Thr
NP_001362274.1:p.Ala312Thr
NP_001362275.1:p.Ala312Thr
NP_001362276.1:p.Ala305Thr
NP_001362277.1:p.Ala194Thr
NP_001362278.1:p.Ala239Thr
NP_001362279.1:p.Ala194Thr
NP_944493.2:p.Ala374Thr
NP_944494.1:p.Ala334Thr
NC_000005.9:g.161576191G>A

Protein change:

A194T

Links:

dbSNP: rs398123523

NCBI 1000 Genomes Browser:

rs398123523

Molecular consequence:

NM_001375340.1:c.923-2545G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000816.3:c.1000G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.991G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.997G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.997G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.1120G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.1039G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.913G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375348.1:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375350.1:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.1120G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.1000G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000111189	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Aug 9, 2013)	germline	clinical testing	Citation Link,
SCV000515993	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 26, 2024)	germline	clinical testing	Citation Link,
SCV004099128	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 13, 2023)	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

SCV000111189

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Aug 9, 2013)

germline

clinical testing

Citation Link,

SCV000515993

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 26, 2024)

germline

clinical testing

Citation Link,

SCV004099128

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 13, 2023)

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	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Eurofins Ntd Llc (ga), SCV000111189.9

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

#	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		2	not provided	not provided	not provided

From GeneDx, SCV000515993.9

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

Description

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: 30190672, 36403551)

#	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 Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV004099128.1

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

Description

PM2

#	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

Last Updated: Apr 13, 2025

ClinVar

Relating variation to medicine