9-98290655-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005458.8(GABBR2):c.2755G>A(p.Val919Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000813 in 1,462,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V919L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

GABBR2
NM_005458.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.65

Publications

2 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023619682).

BP6

Variant 9-98290655-C-T is Benign according to our data. Variant chr9-98290655-C-T is described in ClinVar as Benign. ClinVar VariationId is 580429.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005458.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	NM_005458.8	MANE Select	c.2755G>A	p.Val919Ile	missense	Exon 19 of 19	NP_005449.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GABBR2	ENST00000259455.4	TSL:1 MANE Select	c.2755G>A	p.Val919Ile	missense	Exon 19 of 19	ENSP00000259455.2
GABBR2	ENST00000931526.1		c.2689G>A	p.Val897Ile	missense	Exon 18 of 18	ENSP00000601585.1
GABBR2	ENST00000947376.1		c.2674G>A	p.Val892Ile	missense	Exon 18 of 18	ENSP00000617435.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000127

AC:

AN:

118342

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000782

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000658

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000824

AC:

108

AN:

1310784

Hom.:

Cov.:

AF XY:

0.0000713

AC XY:

AN XY:

645062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25954

American (AMR)

AF:

0.00

AC:

AN:

16948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21002

East Asian (EAS)

AF:

0.000934

AC:

AN:

31050

South Asian (SAS)

AF:

0.000365

AC:

AN:

60248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49884

Middle Eastern (MID)

AF:

0.000197

AC:

AN:

5084

European-Non Finnish (NFE)

AF:

0.0000516

AC:

AN:

1046726

Other (OTH)

AF:

0.0000371

AC:

AN:

53888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000723

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41530

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000580

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000151

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000994

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.031

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.34

PhyloP100

4.7

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.16

REVEL

Benign

0.27

Sift

Uncertain

0.013

Sift4G

Benign

0.11

Polyphen

0.43

Vest4

0.20

MVP

0.52

MPC

0.83

ClinPred

0.042

GERP RS

5.5

Varity_R

0.13

gMVP

0.13

Mutation Taster

=79/21

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over