9-98290667-C-T

Variant names:

• chr9-98290667-C-T
• NM_005458.8:c.2743G>A

Variant summary

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

The NM_005458.8(GABBR2):​c.2743G>A​(p.Val915Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000755 in 1,324,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.6e-7 (0 hom.)
• Consequence: GABBR2 NM_005458.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75

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]

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=0.11053327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.2743G>A	p.Val915Ile	missense_variant	Exon 19 of 19	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.2449G>A	p.Val817Ile	missense_variant	Exon 18 of 18		XP_016870820.1
GABBR2	XM_005252316.6	c.1969G>A	p.Val657Ile	missense_variant	Exon 17 of 17		XP_005252373.1
GABBR2	XM_017015332.3	c.1969G>A	p.Val657Ile	missense_variant	Exon 16 of 16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.2743G>A	p.Val915Ile	missense_variant	Exon 19 of 19	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000637410.1	n.2521G>A		non_coding_transcript_exon_variant	Exon 19 of 19	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1324086 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 653058

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: 9.47e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.24
Sift	Benign	0.071	T
Sift4G	Benign	0.11	T
Polyphen		0.016	B
Vest4		0.044
MutPred		0.13		Loss of glycosylation at S920 (P = 0.0766);
MVP		0.46
MPC		0.75
ClinPred		0.74	D
GERP RS		5.5
Varity_R		0.089
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-101052949;