NM_198904.4(GABRG2):c.1360C>T (p.Arg454Trp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV000645379.8

Allele description [Variation Report for NM_198904.4(GABRG2):c.1360C>T (p.Arg454Trp)]

NM_198904.4(GABRG2):c.1360C>T (p.Arg454Trp)

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.1360C>T (p.Arg454Trp)

Other names:

p.R446W:CGG>TGG

HGVS:

NC_000005.10:g.162153300C>T
NG_009290.1:g.90659C>T
NM_000816.3:c.1336C>T
NM_001375339.1:c.1351C>T
NM_001375340.1:c.*194C>T
NM_001375341.1:c.1357C>T
NM_001375342.1:c.1333C>T
NM_001375343.1:c.1456C>T
NM_001375344.1:c.1399C>T
NM_001375345.1:c.1270C>T
NM_001375346.1:c.1294C>T
NM_001375347.1:c.1273C>T
NM_001375348.1:c.916C>T
NM_001375349.1:c.1051C>T
NM_001375350.1:c.940C>T
NM_198903.2:c.1480C>T
NM_198904.4:c.1360C>TMANE SELECT
NP_000807.2:p.Arg446Trp
NP_001362268.1:p.Arg451Trp
NP_001362270.1:p.Arg453Trp
NP_001362271.1:p.Arg445Trp
NP_001362272.1:p.Arg486Trp
NP_001362273.1:p.Arg467Trp
NP_001362274.1:p.Arg424Trp
NP_001362275.1:p.Arg432Trp
NP_001362276.1:p.Arg425Trp
NP_001362277.1:p.Arg306Trp
NP_001362278.1:p.Arg351Trp
NP_001362279.1:p.Arg314Trp
NP_944493.2:p.Arg494Trp
NP_944494.1:p.Arg454Trp
NC_000005.9:g.161580306C>T

Protein change:

R306W

Links:

dbSNP: rs796052515

NCBI 1000 Genomes Browser:

rs796052515

Molecular consequence:

NM_001375340.1:c.*194C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000816.3:c.1336C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.1351C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.1333C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.1456C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.1399C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.1270C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.1294C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.1273C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375348.1:c.916C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.1051C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375350.1:c.940C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.1480C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.1360C>T - 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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hypothetical protein THAOC_05875 [Thalassiosira oceanica]
hypothetical protein THAOC_05875 [Thalassiosira oceanica]
gi|397637218|gb|EJK72581.1||gnl|WGS |THAOC_05875p

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000767124	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2023)	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

SCV000767124

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2023)

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, SCV000767124.5

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

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. 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. ClinVar contains an entry for this variant (Variation ID: 205556). This missense change has been observed in individual(s) with clinical features of GABRG2-related conditions (PMID: 29655203; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 446 of the GABRG2 protein (p.Arg446Trp).

#	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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