9-98578034-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005458.8(GABBR2):c.360A>G(p.Ala120Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,340 control chromosomes in the GnomAD database, including 24,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2733 hom., cov: 34)

Exomes 𝑓: 0.17 ( 21596 hom. )

Consequence

GABBR2
NM_005458.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.30

Publications

24 publications found

Variant links:

Genes affected

GABBR2 (HGNC:4507): (gamma-aminobutyric acid type B receptor subunit 2) The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]

GABBR2 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 59
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder with poor language and loss of hand skills
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
atypical Rett syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GABBR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 9-98578034-T-C is Benign according to our data. Variant chr9-98578034-T-C is described in ClinVar as Benign. ClinVar VariationId is 132156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8 link	c.360A>G	p.Ala120Ala	synonymous_variant	Exon 2 of 19	ENST00000259455.4	NP_005449.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
GABBR2	ENST00000259455.4 link	c.360A>G	p.Ala120Ala	synonymous_variant	Exon 2 of 19	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000634227.1 link	n.134A>G		non_coding_transcript_exon_variant	Exon 2 of 6	5
GABBR2	ENST00000637410.1 link	n.138A>G		non_coding_transcript_exon_variant	Exon 2 of 19	5
GABBR2	ENST00000637717.1 link	c.-25A>G		5_prime_UTR_variant	Exon 2 of 3	5		ENSP00000490789.1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28229

AN:

152140

Hom.:

2733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.162

AC:

40695

AN:

251194

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.0784

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.168

AC:

245476

AN:

1461082

Hom.:

21596

Cov.:

AF XY:

0.168

AC XY:

121914

AN XY:

726890

show subpopulations

African (AFR)

AF:

0.239

AC:

7996

AN:

33452

American (AMR)

AF:

0.0835

AC:

3734

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

5714

AN:

26126

East Asian (EAS)

AF:

0.175

AC:

6937

AN:

39694

South Asian (SAS)

AF:

0.122

AC:

10527

AN:

86216

European-Finnish (FIN)

AF:

0.188

AC:

10066

AN:

53406

Middle Eastern (MID)

AF:

0.210

AC:

1212

AN:

5766

European-Non Finnish (NFE)

AF:

0.170

AC:

189287

AN:

1111348

Other (OTH)

AF:

0.166

AC:

10003

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

9668

19337

29005

38674

48342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6632

13264

19896

26528

33160

<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:

0.185

AC:

28237

AN:

152258

Hom.:

2733

Cov.:

AF XY:

0.185

AC XY:

13743

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.234

AC:

9699

AN:

41528

American (AMR)

AF:

0.122

AC:

1874

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

778

AN:

3472

East Asian (EAS)

AF:

0.143

AC:

741

AN:

5176

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4830

European-Finnish (FIN)

AF:

0.192

AC:

2035

AN:

10620

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11853

AN:

68014

Other (OTH)

AF:

0.168

AC:

356

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1207

2414

3621

4828

6035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.179

Hom.:

8075

Bravo

AF:

0.183

Asia WGS

AF:

0.140

AC:

487

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.174

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epileptic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over