Variant chr5-162067984-GA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_198904.4(GABRG2):c.-4del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 908,344 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0088 ( 12 hom., cov: 31)

Exomes 𝑓: 0.13 ( 7 hom. )

Consequence

GABRG2
NM_198904.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.142

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 5-162067984-GA-G is Benign according to our data. Variant chr5-162067984-GA-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 352637.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}. Variant chr5-162067984-GA-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG2	NM_198904.4 linkuse as main transcript	c.-4del		5_prime_UTR_variant	1/10	ENST00000639213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG2	ENST00000639213.2 linkuse as main transcript	c.-4del		5_prime_UTR_variant	1/10	1	NM_198904.4	A1	P18507-2

Frequencies

GnomAD3 genomes

AF:

0.00880

AC:

1224

AN:

139092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.000609

Gnomad EAS

AF:

0.000208

Gnomad SAS

AF:

0.000919

Gnomad FIN

AF:

0.00378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000757

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.135

AC:

103691

AN:

769212

Hom.:

Cov.:

AF XY:

0.136

AC XY:

50698

AN XY:

373124

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.149

GnomAD4 genome

AF:

0.00882

AC:

1227

AN:

139132

Hom.:

Cov.:

AF XY:

0.00852

AC XY:

574

AN XY:

67384

show subpopulations

Gnomad4 AFR

AF:

0.0280

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.000609

Gnomad4 EAS

AF:

0.000209

Gnomad4 SAS

AF:

0.00115

Gnomad4 FIN

AF:

0.00378

Gnomad4 NFE

AF:

0.000757

Gnomad4 OTH

AF:

0.00569

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Generalized epilepsy with febrile seizures plus

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Severe myoclonic epilepsy in infancy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2018

This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 21, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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