NM_198904.4(GABRG2):c.1400T>G (p.Val467Gly) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 27, 2023
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:: RCV003797544.2

Allele description [Variation Report for NM_198904.4(GABRG2):c.1400T>G (p.Val467Gly)]

NM_198904.4(GABRG2):c.1400T>G (p.Val467Gly)

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.1400T>G (p.Val467Gly)

HGVS:

NC_000005.10:g.162153340T>G
NG_009290.1:g.90699T>G
NM_000816.3:c.1376T>G
NM_001375339.1:c.1391T>G
NM_001375340.1:c.*234T>G
NM_001375341.1:c.1397T>G
NM_001375342.1:c.1373T>G
NM_001375343.1:c.1496T>G
NM_001375344.1:c.1439T>G
NM_001375345.1:c.1310T>G
NM_001375346.1:c.1334T>G
NM_001375347.1:c.1313T>G
NM_001375348.1:c.956T>G
NM_001375349.1:c.1091T>G
NM_001375350.1:c.980T>G
NM_198903.2:c.1520T>G
NM_198904.4:c.1400T>GMANE SELECT
NP_000807.2:p.Val459Gly
NP_001362268.1:p.Val464Gly
NP_001362270.1:p.Val466Gly
NP_001362271.1:p.Val458Gly
NP_001362272.1:p.Val499Gly
NP_001362273.1:p.Val480Gly
NP_001362274.1:p.Val437Gly
NP_001362275.1:p.Val445Gly
NP_001362276.1:p.Val438Gly
NP_001362277.1:p.Val319Gly
NP_001362278.1:p.Val364Gly
NP_001362279.1:p.Val327Gly
NP_944493.2:p.Val507Gly
NP_944494.1:p.Val467Gly
NC_000005.9:g.161580346T>G

Protein change:

V319G

Molecular consequence:

NM_001375340.1:c.*234T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000816.3:c.1376T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.1391T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.1397T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.1373T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.1496T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.1439T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.1310T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.1334T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.1313T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375348.1:c.956T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.1091T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375350.1:c.980T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.1520T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.1400T>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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Nucleotide
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Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004586685	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 27, 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

SCV004586685

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 27, 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	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, SCV004586685.1

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

Description

This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 459 of the GABRG2 protein (p.Val459Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GABRG2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GABRG2 protein function with a positive predictive value of 95%. 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: Sep 29, 2024

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