rs758345055

Positions:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The NM_005458.8(GABBR2):c.2767G>T(p.Ala923Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,447,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

GABBR2
NM_005458.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.24

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GABBR2. . Gene score misZ 4.6253 (greater than the threshold 3.09). Trascript score misZ 4.0975 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 59, neurodevelopmental disorder with poor language and loss of hand skills, atypical Rett syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.0855262).

BP6

Variant 9-98290643-C-A is Benign according to our data. Variant chr9-98290643-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3340554.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8 linkuse as main transcript	c.2767G>T	p.Ala923Ser	missense_variant	19/19	ENST00000259455.4	NP_005449.5	O75899H9NIL8
GABBR2	XM_017015331.3 linkuse as main transcript	c.2473G>T	p.Ala825Ser	missense_variant	18/18		XP_016870820.1
GABBR2	XM_005252316.6 linkuse as main transcript	c.1993G>T	p.Ala665Ser	missense_variant	17/17		XP_005252373.1
GABBR2	XM_017015332.3 linkuse as main transcript	c.1993G>T	p.Ala665Ser	missense_variant	16/16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 linkuse as main transcript	c.2767G>T	p.Ala923Ser	missense_variant	19/19	1	NM_005458.8	ENSP00000259455.2		O75899
GABBR2	ENST00000637410.1 linkuse as main transcript	n.*4G>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.72e-7

AC:

AN:

1295632

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

635316

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.65e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000605

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 04, 2024

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

Eigen

Benign

-0.064

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.79

M_CAP

Benign

0.015

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.29

REVEL

Benign

0.28

Sift

Benign

0.19

Sift4G

Benign

0.41

Polyphen

0.016

Vest4

0.057

MutPred

0.097

Gain of relative solvent accessibility (P = 0.005);

MVP

0.44

MPC

0.83

ClinPred

0.49

GERP RS

5.5

Varity_R

0.097

gMVP

0.25

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