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NM_198903.2(GABRG2):c.1233_1235del (p.Lys414del)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Sep 29, 2021)
Last evaluated:
Jun 22, 2020
Accession:
VCV000167117.5
Variation ID:
167117
Description:
3bp deletion
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NM_198903.2(GABRG2):c.1233_1235del (p.Lys414del)

Allele ID
177736
Variant type
Deletion
Variant length
3 bp
Cytogenetic location
5q34
Genomic location
5: 162149296-162149298 (GRCh38) GRCh38 UCSC
5: 161576302-161576304 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000816.3:c.1113_1115delAAA
NC_000005.10:g.162149298_162149300del
NC_000005.9:g.161576304_161576306del
... more HGVS
Protein change
K414del, K374del
Other names
-
Canonical SPDI
NC_000005.10:162149295:AAAAA:AA
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA234055
dbSNP: rs727503941
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Aug 23, 2017 RCV000624390.1
Uncertain significance 1 criteria provided, single submitter Jun 22, 2020 RCV001223368.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Aug 30, 2019 RCV000723908.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GABRG2 Little evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
381 409

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Apr 03, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000202771.7
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Likely benign
(Aug 30, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000241137.11
Submitted: (Sep 29, 2021)
Evidence details
Comment:
This variant is associated with the following publications: (PMID: 30660939)
Uncertain significance
(Aug 23, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary disease
Allele origin: germline
Ambry Genetics
Accession: SCV000742820.1
Submitted: (Feb 08, 2018)
Evidence details
Publications
PubMed (16)
Comment:
Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Uncertain significance
(Jun 22, 2020)
criteria provided, single submitter
Method: clinical testing
Familial febrile seizures 8
Epilepsy, childhood absence 2
Allele origin: germline
Invitae
Accession: SCV001395513.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This variant, c.1113_1115del, results in the deletion of 1 amino acid(s) of the GABRG2 protein (p.Lys374del), but otherwise preserves the integrity of the reading frame. … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Genetic testing in a cohort of patients with potential epilepsy with myoclonic-atonic seizures. Angione K Epilepsy research 2019 PMID: 30660939
Expanding the phenotypic spectrum of GABRG2 variants: a recurrent GABRG2 missense variant associated with a severe phenotype. Zou F Journal of neurogenetics 2017 PMID: 28460589
Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation. Kobayashi Y Genome medicine 2017 PMID: 28166811
UniProt: the universal protein knowledgebase. The UniProt Consortium. Nucleic acids research 2017 PMID: 27899622
De novo GABRG2 mutations associated with epileptic encephalopathies. Shen D Brain : a journal of neurology 2017 PMID: 27864268
Molecular Pathogenic Basis for GABRG2 Mutations Associated With a Spectrum of Epilepsy Syndromes, From Generalized Absence Epilepsy to Dravet Syndrome. Kang JQ JAMA neurology 2016 PMID: 27367160
Differential molecular and behavioural alterations in mouse models of GABRG2 haploinsufficiency versus dominant negative mutations associated with human epilepsy. Warner TA Human molecular genetics 2016 PMID: 27340224
Novel GABRG2 mutations cause familial febrile seizures. Boillot M Neurology. Genetics 2015 PMID: 27066572
Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes. Reinthaler EM Annals of neurology 2015 PMID: 25726841
Association of nonsense mutation in GABRG2 with abnormal trafficking of GABAA receptors in severe epilepsy. Ishii A Epilepsy research 2014 PMID: 24480790
A novel GABRG2 mutation, p.R136*, in a family with GEFS+ and extended phenotypes. Johnston AJ Neurobiology of disease 2014 PMID: 24407264
GABA(A) receptor alpha1 subunit mutation A322D associated with autosomal dominant juvenile myoclonic epilepsy reduces the expression and alters the composition of wild type GABA(A) receptors. Ding L The Journal of biological chemistry 2010 PMID: 20551311
Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies. Shi X Journal of human genetics 2010 PMID: 20485450
A novel GABRG2 mutation associated with febrile seizures. Audenaert D Neurology 2006 PMID: 16924025
Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation. Marini C Brain : a journal of neurology 2003 PMID: 12477709
Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus. Harkin LA American journal of human genetics 2002 PMID: 11748509
Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. Wallace RH Nature genetics 2001 PMID: 11326275
First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Baulac S Nature genetics 2001 PMID: 11326274
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GABRG2 - - - -

Text-mined citations for rs727503941...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2021