6-89299793-G-T

Variant names:

• chr6-89299793-G-T
• rs34617047
• NM_002043.5:c.186C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002043.5(GABRR2):​c.186C>A​(p.Asp62Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GABRR2 NM_002043.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09333122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.186C>A	p.Asp62Glu	missense_variant	Exon 2 of 9	ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.261C>A	p.Asp87Glu	missense_variant	Exon 2 of 10		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.186C>A	p.Asp62Glu	missense_variant	Exon 2 of 9	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.320C>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251172 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461532 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727068

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.0020
DANN	Benign	0.88
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.41	T
REVEL	Benign	0.051
Sift4G	Benign	1.0	T
Vest4		0.26
MVP		0.54
MPC		0.15
ClinPred		0.096	T
GERP RS		-11
Varity_R		0.053
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs34617047; hg19: chr6-90009512;