NM_198904.4(GABRG2):c.1045G>A (p.Ala349Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 28, 2020
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:: RCV001066010.8

Allele description [Variation Report for NM_198904.4(GABRG2):c.1045G>A (p.Ala349Thr)]

NM_198904.4(GABRG2):c.1045G>A (p.Ala349Thr)

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.1045G>A (p.Ala349Thr)

HGVS:

NC_000005.10:g.162149230G>A
NG_009290.1:g.86589G>A
NM_000816.3:c.1045G>A
NM_001375339.1:c.1036G>A
NM_001375340.1:c.923-2500G>A
NM_001375341.1:c.1042G>A
NM_001375342.1:c.1042G>A
NM_001375343.1:c.1165G>A
NM_001375344.1:c.1084G>A
NM_001375345.1:c.979G>A
NM_001375346.1:c.979G>A
NM_001375347.1:c.958G>A
NM_001375348.1:c.625G>A
NM_001375349.1:c.760G>A
NM_001375350.1:c.625G>A
NM_198903.2:c.1165G>A
NM_198904.4:c.1045G>AMANE SELECT
NP_000807.2:p.Ala349Thr
NP_001362268.1:p.Ala346Thr
NP_001362270.1:p.Ala348Thr
NP_001362271.1:p.Ala348Thr
NP_001362272.1:p.Ala389Thr
NP_001362273.1:p.Ala362Thr
NP_001362274.1:p.Ala327Thr
NP_001362275.1:p.Ala327Thr
NP_001362276.1:p.Ala320Thr
NP_001362277.1:p.Ala209Thr
NP_001362278.1:p.Ala254Thr
NP_001362279.1:p.Ala209Thr
NP_944493.2:p.Ala389Thr
NP_944494.1:p.Ala349Thr
NC_000005.9:g.161576236G>A

Protein change:

A209T

Links:

dbSNP: rs756959300

NCBI 1000 Genomes Browser:

rs756959300

Molecular consequence:

NM_001375340.1:c.923-2500G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000816.3:c.1045G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.1036G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.1042G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.1042G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.1165G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.1084G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.958G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375348.1:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.760G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375350.1:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.1165G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.1045G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Epilepsy, childhood absence 2 (ECA2)
Identifiers:: MedGen: C1843244; Orphanet: 64280

Name:: Febrile seizures, familial, 8 (FEB8)
Synonyms:: CONVULSIONS, FAMILIAL FEBRILE, 8
Identifiers:: MONDO: MONDO:0011891; MedGen: C1969810; Orphanet: 36387; OMIM: 607681

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001231003	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2020)	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

SCV001231003

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001231003.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GABRG2-related conditions. This variant is present in population databases (rs756959300, ExAC 0.01%). This sequence change replaces alanine with threonine at codon 349 of the GABRG2 protein (p.Ala349Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.

#	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: Sep 29, 2024

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