2-96114968-T-G

Variant names:

• chr2-96114968-T-G
• rs2229169
• NM_000682.7:c.1182A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 publications found

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]

ADRA2B Gene-Disease associations (from GenCC):

• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P
• epilepsy, familial adult myoclonic, 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000682.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA2B	NM_000682.7	MANE Select	c.1182A>C	p.Gly394Gly	synonymous	Exon 1 of 1	NP_000673.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA2B	ENST00000620793.2	TSL:6 MANE Select	c.1182A>C	p.Gly394Gly	synonymous	Exon 1 of 1	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

GnomAD2 exomes AF: 0.673 AC: 164882 AN: 245152 AF XY: 0.680

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 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

African (AFR) AF: 0.745 AC: 24930 AN: 33462

American (AMR) AF: 0.658 AC: 29228 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 20843 AN: 26108

East Asian (EAS) AF: 0.600 AC: 23773 AN: 39644

South Asian (SAS) AF: 0.773 AC: 66609 AN: 86154

European-Finnish (FIN) AF: 0.539 AC: 28692 AN: 53244

Middle Eastern (MID) AF: 0.850 AC: 4901 AN: 5766

European-Non Finnish (NFE) AF: 0.666 AC: 739521 AN: 1111138

Other (OTH) AF: 0.701 AC: 42291 AN: 60308

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

African (AFR) AF: 0.739 AC: 30671 AN: 41504

American (AMR) AF: 0.695 AC: 10635 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2776 AN: 3468

East Asian (EAS) AF: 0.573 AC: 2949 AN: 5146

South Asian (SAS) AF: 0.780 AC: 3766 AN: 4830

European-Finnish (FIN) AF: 0.536 AC: 5674 AN: 10592

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45484 AN: 67980

Other (OTH) AF: 0.732 AC: 1547 AN: 2114

Alfa AF: 0.687 Hom.: 53924

Bravo AF: 0.694

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.044
DANN	Benign	0.64
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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