2-96114968-T-G

Position:

• chr2-96114968-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000682.7(ADRA2B):​c.1182A>C​(p.Gly394Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,612,352 control chromosomes in the GnomAD database, including 367,634 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (36094 hom., cov: 34)
  • Exomes 𝑓: 0.67 (331540 hom.)
• Consequence: ADRA2B NM_000682.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

Genes affected

ADRA2B (HGNC:282): (adrenoceptor alpha 2B) This intronless gene encodes a seven-pass transmembrane protein. This protein is a member of a subfamily of G protein-coupled receptors that regulate neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-2.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2B	NM_000682.7	c.1182A>C	p.Gly394Gly	synonymous_variant	1/1	ENST00000620793.2	NP_000673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793.2	c.1182A>C	p.Gly394Gly	synonymous_variant	1/1	6	NM_000682.7	ENSP00000480573.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104208 AN: 152020 Hom.: 36081 Cov.: 34

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.730

GnomAD3 exomes AF: 0.673 AC: 164882 AN: 245152 Hom.: 56150 AF XY: 0.680 AC XY: 90594 AN XY: 133196

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.658

Gnomad ASJ exome AF: 0.799

Gnomad EAS exome AF: 0.557

Gnomad SAS exome AF: 0.776

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.672 AC: 980788 AN: 1460214 Hom.: 331540 Cov.: 82 AF XY: 0.676 AC XY: 491017 AN XY: 726302

Gnomad4 AFR exome AF: 0.745

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.798

Gnomad4 EAS exome AF: 0.600

Gnomad4 SAS exome AF: 0.773

Gnomad4 FIN exome AF: 0.539

Gnomad4 NFE exome AF: 0.666

Gnomad4 OTH exome AF: 0.701

GnomAD4 genome AF: 0.685 AC: 104264 AN: 152138 Hom.: 36094 Cov.: 34 AF XY: 0.681 AC XY: 50640 AN XY: 74358

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.732

Alfa AF: 0.686 Hom.: 43136

Bravo AF: 0.694

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.044
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs2229169; hg19: chr2-96780716; COSMIC: COSV69787299;