NM_005458.8:c.2052C>T

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.2052C>T(p.Pro684Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,292 control chromosomes in the GnomAD database, including 22,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2178 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20317 hom. )

Consequence

GABBR2
NM_005458.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.14

Publications

16 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=-0.81).

BP6

Variant 9-98306298-G-A is Benign according to our data. Variant chr9-98306298-G-A is described in ClinVar as Benign. ClinVar VariationId is 1167956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8 link	c.2052C>T	p.Pro684Pro	synonymous_variant	Exon 15 of 19	ENST00000259455.4	NP_005449.5	O75899H9NIL8
GABBR2	XM_017015331.3 link	c.1758C>T	p.Pro586Pro	synonymous_variant	Exon 14 of 18		XP_016870820.1
GABBR2	XM_005252316.6 link	c.1278C>T	p.Pro426Pro	synonymous_variant	Exon 13 of 17		XP_005252373.1
GABBR2	XM_017015332.3 link	c.1278C>T	p.Pro426Pro	synonymous_variant	Exon 12 of 16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 link	c.2052C>T	p.Pro684Pro	synonymous_variant	Exon 15 of 19	1	NM_005458.8	ENSP00000259455.2		O75899

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25174

AN:

152084

Hom.:

2181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.170

AC:

42575

AN:

251022

AF XY:

0.172

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.166

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.164

AC:

240257

AN:

1461090

Hom.:

20317

Cov.:

AF XY:

0.166

AC XY:

120679

AN XY:

726900

show subpopulations

African (AFR)

AF:

0.170

AC:

5675

AN:

33464

American (AMR)

AF:

0.193

AC:

8617

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

3398

AN:

26128

East Asian (EAS)

AF:

0.174

AC:

6920

AN:

39696

South Asian (SAS)

AF:

0.212

AC:

18289

AN:

86218

European-Finnish (FIN)

AF:

0.134

AC:

7132

AN:

53412

Middle Eastern (MID)

AF:

0.267

AC:

1538

AN:

5766

European-Non Finnish (NFE)

AF:

0.161

AC:

178396

AN:

1111350

Other (OTH)

AF:

0.170

AC:

10292

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

10694

21387

32081

42774

53468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6528

13056

19584

26112

32640

<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:

0.165

AC:

25177

AN:

152202

Hom.:

2178

Cov.:

AF XY:

0.165

AC XY:

12267

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.171

AC:

7108

AN:

41528

American (AMR)

AF:

0.191

AC:

2923

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

454

AN:

3470

East Asian (EAS)

AF:

0.173

AC:

896

AN:

5172

South Asian (SAS)

AF:

0.211

AC:

1017

AN:

4826

European-Finnish (FIN)

AF:

0.133

AC:

1413

AN:

10594

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.158

AC:

10738

AN:

68006

Other (OTH)

AF:

0.186

AC:

393

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1112

2224

3335

4447

5559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.163

Hom.:

6232

Bravo

AF:

0.169

Asia WGS

AF:

0.169

AC:

588

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.171

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Neurodevelopmental disorder with poor language and loss of hand skills

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

- -

Developmental and epileptic encephalopathy, 59

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

-0.81

CADD

Benign

1.3

(source)

DANN

Benign

0.77

PhyloP100

-2.1

Mutation Taster

=99/1

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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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