NM_198903.2(GABRG2):c.1208G>A (p.Arg403Gln) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Nov 8, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000645378.2

Allele description [Variation Report for NM_198903.2(GABRG2):c.1208G>A (p.Arg403Gln)]

NM_198903.2(GABRG2):c.1208G>A (p.Arg403Gln)

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_198903.2(GABRG2):c.1208G>A (p.Arg403Gln)
Other names:
p.R363Q:CGG>CAG
HGVS:
  • NC_000005.10:g.162149273G>A
  • NG_009290.1:g.86632G>A
  • NM_000816.3:c.1088G>A
  • NM_198903.2:c.1208G>A
  • NM_198904.2:c.1088G>A
  • NP_000807.2:p.Arg363Gln
  • NP_944493.2:p.Arg403Gln
  • NP_944494.1:p.Arg363Gln
  • NC_000005.9:g.161576279G>A
Protein change:
R363Q
Links:
dbSNP: rs780199000
NCBI 1000 Genomes Browser:
rs780199000
Molecular consequence:
  • NM_000816.3:c.1088G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198903.2:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198904.2:c.1088G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Epilepsy, childhood absence 2 (ECA2)
Synonyms:
Febrile seizures, familial, 8
Identifiers:
MONDO: MONDO:0011891; MedGen: C1843244; Orphanet: 64280; OMIM: 607681
Name:
Familial febrile seizures 8 (FEB8)
Synonyms:
CONVULSIONS, FAMILIAL FEBRILE, 8
Identifiers:
MedGen: C1969810; Orphanet: 36387

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000767123Invitaecriteria provided, single submitter
Uncertain significance
(Nov 8, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

[Clinical, electroencephalographic and genomic characteristics of patients with epilepsy with febrile seizures plus].

Cantarín-Extremera V, García-Peñas JJ, Gutiérrez-Solana LG, García-Fernández M, Ruiz-Falcó ML, Duat-Rodríguez A, López-Marín L.

Rev Neurol. 2011 Apr 1;52(7):404-11. Spanish.

PubMed [citation]
PMID:
21425109

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000767123.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with glutamine at codon 363 of the GABRG2 protein (p.Arg363Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs780199000, ExAC 0.001%). This variant has been reported in an individual affected with epilepsy and febrile seizures (PMID: 21425109). ClinVar contains an entry for this variant (Variation ID: 205564). 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. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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