dbSNP rs548583: GABRA2:c.*554T>C (chr4-46261327-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000515082.5(GABRA2):c.*554T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,916 control chromosomes in the GnomAD database, including 27,860 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 0.60 ( 27740 hom., cov: 33)

Exomes 𝑓: 0.51 ( 120 hom. )

Consequence

GABRA2
ENST00000515082.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.278

Publications

9 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4 link	c.1059+599T>C		intron_variant	Intron 9 of 9	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9 link	c.1059+599T>C		intron_variant	Intron 9 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91160

AN:

151848

Hom.:

27725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.693

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.762

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.640

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.611

GnomAD4 exome

AF:

0.508

AC:

483

AN:

950

Hom.:

120

Cov.:

AF XY:

0.525

AC XY:

274

AN XY:

522

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.489

AC:

AN:

180

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.444

AC:

AN:

South Asian (SAS)

AF:

0.724

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.486

AC:

312

AN:

642

Other (OTH)

AF:

0.538

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.600

AC:

91214

AN:

151966

Hom.:

27740

Cov.:

AF XY:

0.601

AC XY:

44604

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.655

AC:

27191

AN:

41502

American (AMR)

AF:

0.543

AC:

8270

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2403

AN:

3468

East Asian (EAS)

AF:

0.550

AC:

2831

AN:

5150

South Asian (SAS)

AF:

0.762

AC:

3675

AN:

4822

European-Finnish (FIN)

AF:

0.585

AC:

6179

AN:

10564

Middle Eastern (MID)

AF:

0.623

AC:

182

AN:

292

European-Non Finnish (NFE)

AF:

0.569

AC:

38626

AN:

67914

Other (OTH)

AF:

0.612

AC:

1293

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1899

3798

5698

7597

9496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.588

Hom.:

13501

Bravo

AF:

0.593

Asia WGS

AF:

0.642

AC:

2232

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.1

(source)

DANN

Benign

0.51

PhyloP100

0.28

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over