dbSNP rs282129: GABRR2:p.Thr430Met (chr6-89257779-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002043.5(GABRR2):c.1289C>T(p.Thr430Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,613,486 control chromosomes in the GnomAD database, including 65,810 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7447 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58363 hom. )

Consequence

GABRR2
NM_002043.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

GABRR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.2558393E-4).

BP6

Variant 6-89257779-G-A is Benign according to our data. Variant chr6-89257779-G-A is described in ClinVar as [Benign]. Clinvar id is 1286404.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5 link	c.1289C>T	p.Thr430Met	missense_variant	Exon 9 of 9	ENST00000402938.4	NP_002034.3	P28476-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4 link	c.1289C>T	p.Thr430Met	missense_variant	Exon 9 of 9	1	NM_002043.5	ENSP00000386029.4		P28476-1
GABRR2	ENST00000602432.1 link	n.1120C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45865

AN:

151960

Hom.:

7448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.248

AC:

62126

AN:

250866

Hom.:

8434

AF XY:

0.245

AC XY:

33176

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.430

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.143

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.277

AC:

405262

AN:

1461406

Hom.:

58363

Cov.:

AF XY:

0.274

AC XY:

199125

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.436

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.302

AC:

45890

AN:

152080

Hom.:

7447

Cov.:

AF XY:

0.296

AC XY:

21982

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.275

Hom.:

15019

Bravo

AF:

0.299

TwinsUK

AF:

0.276

AC:

1023

ALSPAC

AF:

0.288

AC:

1109

ESP6500AA

AF:

0.426

AC:

1877

ESP6500EA

AF:

0.279

AC:

2397

ExAC

AF:

0.255

AC:

30947

Asia WGS

AF:

0.186

AC:

649

AN:

3478

EpiCase

AF:

0.268

EpiControl

AF:

0.260

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19536785) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.016

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.29

MetaRNN

Benign

0.00083

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.28

REVEL

Benign

0.13

Sift4G

Benign

0.13

Vest4

0.021

MPC

0.15

ClinPred

0.010

GERP RS

3.5

Varity_R

0.015

gMVP

0.42

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