rs41311629

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_198903.2(GABRG2):c.703G>T(p.Gly235Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 453,378 control chromosomes in the GnomAD database, including 2,565 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G235G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.11 ( 912 hom., cov: 32)

Exomes 𝑓: 0.10 ( 1653 hom. )

Consequence

GABRG2
NM_198903.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.504

Variant links:

Genes affected

GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in the GABRG2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 34 curated pathogenic missense variants (we use a threshold of 10). The gene has 21 curated benign missense variants. Gene score misZ: 2.9939 (below the threshold of 3.09). Trascript score misZ: 3.9088 (above the threshold of 3.09). GenCC associations: The gene is linked to epilepsy, Dravet syndrome, undetermined early-onset epileptic encephalopathy, generalized epilepsy with febrile seizures plus, developmental and epileptic encephalopathy, 74, febrile seizures, familial, 8, childhood epilepsy with centrotemporal spikes.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018987358).

BP6

Variant 5-162102625-G-T is Benign according to our data. Variant chr5-162102625-G-T is described in ClinVar as [Benign]. Clinvar id is 585904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG2	NM_198904.4 link	c.632-1264G>T		intron_variant	Intron 5 of 9	ENST00000639213.2	NP_944494.1	P18507-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000639213.2 link	c.632-1264G>T		intron_variant	Intron 5 of 9	1	NM_198904.4	ENSP00000491909.2		P18507-2

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16230

AN:

151778

Hom.:

912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.0883

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0641

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.0969

AC:

12418

AN:

128194

Hom.:

639

AF XY:

0.0983

AC XY:

6897

AN XY:

70192

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0666

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0656

Gnomad SAS exome

AF:

0.0977

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.101

AC:

30468

AN:

301482

Hom.:

1653

Cov.:

AF XY:

0.102

AC XY:

17545

AN XY:

171808

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.0661

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.0656

Gnomad4 SAS exome

AF:

0.0979

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

AF:

0.107

AC:

16237

AN:

151896

Hom.:

912

Cov.:

AF XY:

0.106

AC XY:

7892

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0882

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.0643

Gnomad4 SAS

AF:

0.0958

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.108

Hom.:

160

Bravo

AF:

0.104

TwinsUK

AF:

0.104

AC:

386

ALSPAC

AF:

0.105

AC:

405

ExAC

AF:

0.0864

AC:

1247

Asia WGS

AF:

0.0840

AC:

293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 14, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.0

DANN

Benign

0.24

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0055

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.29

N;.

REVEL

Benign

0.047

Sift

Uncertain

0.0060

D;.

Sift4G

Benign

0.064

T;.

Vest4

0.060

MPC

1.4

ClinPred

0.0020

GERP RS

-0.45

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over