Variant 9-98306298-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

GABBR2 (HGNC:):

GABBR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8 linkuse as main transcript	c.2052C>T	p.Pro684Pro	synonymous_variant	15/19	ENST00000259455.4	NP_005449.5	O75899H9NIL8
GABBR2	XM_017015331.3 linkuse as main transcript	c.1758C>T	p.Pro586Pro	synonymous_variant	14/18		XP_016870820.1
GABBR2	XM_005252316.6 linkuse as main transcript	c.1278C>T	p.Pro426Pro	synonymous_variant	13/17		XP_005252373.1
GABBR2	XM_017015332.3 linkuse as main transcript	c.1278C>T	p.Pro426Pro	synonymous_variant	12/16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 linkuse as main transcript	c.2052C>T	p.Pro684Pro	synonymous_variant	15/19	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

GnomAD3 exomes

AF:

0.170

AC:

42575

AN:

251022

Hom.:

3815

AF XY:

0.172

AC XY:

23361

AN XY:

135692

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 SAS exome

AF:

0.218

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

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.174

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.165

AC:

25177

AN:

152202

Hom.:

2178

Cov.:

AF XY:

0.165

AC XY:

12267

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.165

Hom.:

2791

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Neurodevelopmental disorder with poor language and loss of hand skills

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 59

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.77

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