NM_198904.4(GABRG2):c.419A>G (p.Asn140Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 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:: RCV001981833.7

Allele description [Variation Report for NM_198904.4(GABRG2):c.419A>G (p.Asn140Ser)]

NM_198904.4(GABRG2):c.419A>G (p.Asn140Ser)

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.419A>G (p.Asn140Ser)

HGVS:

NC_000005.10:g.162097729A>G
NG_009290.1:g.35088A>G
NM_000816.3:c.419A>G
NM_001375339.1:c.410A>G
NM_001375340.1:c.419A>G
NM_001375341.1:c.419A>G
NM_001375342.1:c.419A>G
NM_001375343.1:c.419A>G
NM_001375344.1:c.419A>G
NM_001375345.1:c.353A>G
NM_001375346.1:c.353A>G
NM_001375347.1:c.332A>G
NM_001375348.1:c.-2A>G
NM_001375349.1:c.134A>G
NM_001375350.1:c.-2A>G
NM_198903.2:c.419A>G
NM_198904.4:c.419A>GMANE SELECT
NP_000807.2:p.Asn140Ser
NP_001362268.1:p.Asn137Ser
NP_001362269.1:p.Asn140Ser
NP_001362270.1:p.Asn140Ser
NP_001362271.1:p.Asn140Ser
NP_001362272.1:p.Asn140Ser
NP_001362273.1:p.Asn140Ser
NP_001362274.1:p.Asn118Ser
NP_001362275.1:p.Asn118Ser
NP_001362276.1:p.Asn111Ser
NP_001362278.1:p.Asn45Ser
NP_944493.2:p.Asn140Ser
NP_944494.1:p.Asn140Ser
NC_000005.9:g.161524735A>G

Protein change:

N111S

Links:

dbSNP: rs1554097879

NCBI 1000 Genomes Browser:

rs1554097879

Molecular consequence:

NM_001375348.1:c.-2A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001375350.1:c.-2A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000816.3:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.410A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375340.1:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.353A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.353A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.332A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.134A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.419A>G - 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
SCV002216802	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29655203, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002216802

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2020)

germline

clinical testing

PubMed (2)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA.

Epilepsia. 2018 May;59(5):1062-1071. doi: 10.1111/epi.14074. Epub 2018 Apr 14.

PubMed [citation]

PMID:: 29655203

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, SCV002216802.4

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

Description

This sequence change replaces asparagine with serine at codon 140 of the GABRG2 protein (p.Asn140Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of GABRG2-related conditions (PMID: 29655203, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

#	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: Mar 5, 2025

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