VCV000521624.2 - ClinVar

NM_198904.4(GABRG2):c.1140G>A (p.Met380Ile)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_198904.4(GABRG2):c.1140G>A (p.Met380Ile)

Variation ID: 521624 Accession: VCV000521624.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q34 5: 162151741 (GRCh38) [ NCBI UCSC ] 5: 161578747 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 15, 2018	Dec 11, 2022	Apr 28, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_198904.4:c.1140G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_944494.1:p.Met380Ile	missense
NM_000816.3:c.1129-1352G>A		intron variant
NM_001375339.1:c.1131G>A	NP_001362268.1:p.Met377Ile	missense
NM_001375340.1:c.934G>A	NP_001362269.1:p.Val312Ile	missense
NM_001375341.1:c.1137G>A	NP_001362270.1:p.Met379Ile	missense
NM_001375342.1:c.1126-1352G>A		intron variant
NM_001375343.1:c.1249-1352G>A		intron variant
NM_001375344.1:c.1179G>A	NP_001362273.1:p.Met393Ile	missense
NM_001375345.1:c.1063-1352G>A		intron variant
NM_001375346.1:c.1074G>A	NP_001362275.1:p.Met358Ile	missense
NM_001375347.1:c.1053G>A	NP_001362276.1:p.Met351Ile	missense
NM_001375348.1:c.709-1352G>A		intron variant
NM_001375349.1:c.844-1352G>A		intron variant
NM_001375350.1:c.720G>A	NP_001362279.1:p.Met240Ile	missense
NM_198903.2:c.1260G>A	NP_944493.2:p.Met420Ile	missense
NC_000005.10:g.162151741G>A
NC_000005.9:g.161578747G>A
NG_009290.1:g.89100G>A

... more HGVS ... less HGVS

Protein change

M420I, M380I, M240I, M351I, M358I, M377I, M379I, M393I, V312I

Other names

Canonical SPDI

NC_000005.10:162151740:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA362182783 dbSNP: rs1554101092 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GABRG2		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	677	713

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Apr 28, 2017	RCV000622332.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Apr 28, 2017)	criteria provided, single submitter (ambry_reporting_categories_2017) Method: clinical testing	Hereditary disease Affected status: yes Allele origin: germline	Ambry Genetics Accession: SCV000742293.2 First in ClinVar: Apr 15, 2018 Last updated: Dec 11, 2022	Publications: PubMed (16) PubMed: 20485450‚ 11326274‚ 16924025‚ 11748509‚ 12477709‚ 11326275‚ 27340224‚ 27066572‚ 20551311‚ 24480790‚ 27367160‚ 24407264‚ 25726841‚ 27864268‚ 28460589‚ 27899622 Comment: Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected Clinical Features: Seizures/Epilepsy (present) , Dermatologic (adult onset) (present) , Gastrointestinal (adult onset) (present) , Musculoskeletal/Structural (adult onset) (present) , Neurologic (child onset) (present) Family history: yes Sex: female Segregation observed: yes

Germline Functional Evidence

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 germline classification of this variant

Title	Author	Journal	Year	Link
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
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
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Text-mined citations for rs1554101092 ...

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 Dec 11, 2022

ClinVar Genomic variation as it relates to human health

NM_198904.4(GABRG2):c.1140G>A (p.Met380Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1554101092 ...