dbSNP rs16859227: GABRA2:c.*1720G>A (chr4-46248588-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_000807.4(GABRA2):c.*1720G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,176 control chromosomes in the GnomAD database, including 3,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3315 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

GABRA2
NM_000807.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555

Publications

4 publications found

Variant links:

Genes affected

GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

GABRA2 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 78
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GABRA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4 link	c.*1720G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000381620.9	NP_000798.2	P47869-1A0A024R9X6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GABRA2	ENST00000381620.9 link	c.*1720G>A	3_prime_UTR_variant	Exon 10 of 10	1	NM_000807.4	ENSP00000371033.4	P47869-1
GABRA2	ENST00000510861.5 link	c.*1720G>A	3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000421828.1	P47869-1
GABRA2	ENST00000514090.5 link	c.*1720G>A	3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000421300.1	P47869-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30072

AN:

151058

Hom.:

3313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.0990

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.217

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.199

AC:

30094

AN:

151176

Hom.:

3315

Cov.:

AF XY:

0.195

AC XY:

14393

AN XY:

73816

show subpopulations

African (AFR)

AF:

0.142

AC:

5881

AN:

41400

American (AMR)

AF:

0.235

AC:

3550

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

714

AN:

3444

East Asian (EAS)

AF:

0.0592

AC:

301

AN:

5088

South Asian (SAS)

AF:

0.0991

AC:

477

AN:

4814

European-Finnish (FIN)

AF:

0.164

AC:

1729

AN:

10556

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16651

AN:

67478

Other (OTH)

AF:

0.218

AC:

457

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1206

2413

3619

4826

6032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.237

Hom.:

6824

Bravo

AF:

0.206

Asia WGS

AF:

0.0880

AC:

306

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs16859227

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over