NM_198903.2(GABRG2):c.1181G>T (p.Gly394Val) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Apr 19, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000467084.2

Allele description [Variation Report for NM_198903.2(GABRG2):c.1181G>T (p.Gly394Val)]

NM_198903.2(GABRG2):c.1181G>T (p.Gly394Val)

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.1181G>T (p.Gly394Val)
HGVS:
  • NC_000005.10:g.162149246G>T
  • NG_009290.1:g.86605G>T
  • NM_000816.3:c.1061G>T
  • NM_198903.2:c.1181G>T
  • NM_198904.2:c.1061G>T
  • NP_000807.2:p.Gly354Val
  • NP_944493.2:p.Gly394Val
  • NP_944494.1:p.Gly354Val
  • NC_000005.9:g.161576252G>T
Protein change:
G354V
Links:
dbSNP: rs1060501888
NCBI 1000 Genomes Browser:
rs1060501888
Molecular consequence:
  • NM_000816.3:c.1061G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198903.2:c.1181G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198904.2:c.1061G>T - 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
SCV000547788Invitaecriteria provided, single submitter
Likely pathogenic
(Apr 19, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000547788.3

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

Description

This sequence change replaces glycine with valine at codon 354 of the GABRG2 protein (p.Gly354Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with epilepsy (Invitae database). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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