NM_198904.4(GABRG2):c.967C>T (p.Arg323Trp) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: May 27, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000196679.4

Allele description [Variation Report for NM_198904.4(GABRG2):c.967C>T (p.Arg323Trp)]

NM_198904.4(GABRG2):c.967C>T (p.Arg323Trp)

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.967C>T (p.Arg323Trp)
Other names:
p.R323W:CGG>TGG
HGVS:
  • NC_000005.10:g.162149152C>T
  • NG_009290.1:g.86511C>T
  • NM_000816.3:c.967C>T
  • NM_000816.3:c.967C>T
  • NM_001375339.1:c.958C>T
  • NM_001375340.1:c.923-2578C>T
  • NM_001375341.1:c.964C>T
  • NM_001375342.1:c.964C>T
  • NM_001375343.1:c.1087C>T
  • NM_001375344.1:c.1006C>T
  • NM_001375345.1:c.901C>T
  • NM_001375346.1:c.901C>T
  • NM_001375347.1:c.880C>T
  • NM_001375348.1:c.547C>T
  • NM_001375349.1:c.682C>T
  • NM_001375350.1:c.547C>T
  • NM_198903.2:c.1087C>T
  • NM_198903.2:c.1087C>T
  • NM_198904.4:c.967C>TMANE SELECT
  • NP_000807.2:p.Arg323Trp
  • NP_000807.2:p.Arg323Trp
  • NP_001362268.1:p.Arg320Trp
  • NP_001362270.1:p.Arg322Trp
  • NP_001362271.1:p.Arg322Trp
  • NP_001362272.1:p.Arg363Trp
  • NP_001362273.1:p.Arg336Trp
  • NP_001362274.1:p.Arg301Trp
  • NP_001362275.1:p.Arg301Trp
  • NP_001362276.1:p.Arg294Trp
  • NP_001362277.1:p.Arg183Trp
  • NP_001362278.1:p.Arg228Trp
  • NP_001362279.1:p.Arg183Trp
  • NP_944493.2:p.Arg363Trp
  • NP_944493.2:p.Arg363Trp
  • NP_944494.1:p.Arg323Trp
  • NC_000005.9:g.161576158C>T
  • NC_000005.9:g.161576158C>T
Protein change:
R183W
Links:
dbSNP: rs796052510
NCBI 1000 Genomes Browser:
rs796052510
Molecular consequence:
  • NM_001375340.1:c.923-2578C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000816.3:c.967C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375339.1:c.958C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375341.1:c.964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375342.1:c.964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375343.1:c.1087C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375344.1:c.1006C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375345.1:c.901C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375346.1:c.901C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375347.1:c.880C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375348.1:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375349.1:c.682C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375350.1:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198903.2:c.1087C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198904.4:c.967C>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
SCV000254658Invitaecriteria provided, single submitter
Pathogenic
(May 27, 2019)
germlineclinical testing

PubMed (3)
[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

De novo GABRG2 mutations associated with epileptic encephalopathies.

Shen D, Hernandez CC, Shen W, Hu N, Poduri A, Shiedley B, Rotenberg A, Datta AN, Leiz S, Patzer S, Boor R, Ramsey K, Goldberg E, Helbig I, Ortiz-Gonzalez XR, Lemke JR, Marsh ED, Macdonald RL.

Brain. 2017 Jan;140(1):49-67. doi: 10.1093/brain/aww272. Epub 2016 Nov 17.

PubMed [citation]
PMID:
27864268
PMCID:
PMC5226060

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, et al.

Nat Genet. 2013 Jul;45(7):825-30. doi: 10.1038/ng.2646. Epub 2013 May 26.

PubMed [citation]
PMID:
23708187
PMCID:
PMC3704157
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000254658.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with tryptophan at codon 323 of the GABRG2 protein (p.Arg323Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with early-onset epilepsy (PMID: 27864268) and has been observed to segregate with disease in a family (Invitae). This variant has been reported to affect GABRG2 protein function (PMID: 27864268). This variant disrupts the p.Arg323 amino acid residue in GABRG2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23708187). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 25, 2021

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