2-96116247-G-C

Variant names:

• chr2-96116247-G-C
• rs3111873
• NM_000682.7:c.-98C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000682.7(ADRA2B):​c.-98C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,150,960 control chromosomes in the GnomAD database, including 271,113 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 0.71 (39520 hom., cov: 33)
  • Exomes 𝑓: 0.68 (231593 hom.)
• Consequence: ADRA2B NM_000682.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 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.-98C>G		5_prime_UTR	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.-98C>G		5_prime_UTR	Exon 1 of 1	ENSP00000480573.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108488 AN: 151934 Hom.: 39495 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.678 AC: 676871 AN: 998908 Hom.: 231593 Cov.: 13 AF XY: 0.682 AC XY: 344858 AN XY: 505316

African (AFR) AF: 0.852 AC: 19950 AN: 23414

American (AMR) AF: 0.675 AC: 21220 AN: 31430

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 17518 AN: 21916

East Asian (EAS) AF: 0.606 AC: 20421 AN: 33720

South Asian (SAS) AF: 0.776 AC: 53887 AN: 69436

European-Finnish (FIN) AF: 0.542 AC: 25053 AN: 46242

Middle Eastern (MID) AF: 0.855 AC: 2829 AN: 3310

European-Non Finnish (NFE) AF: 0.668 AC: 484648 AN: 725256

Other (OTH) AF: 0.709 AC: 31345 AN: 44184

GnomAD4 genome AF: 0.714 AC: 108565 AN: 152052 Hom.: 39520 Cov.: 33 AF XY: 0.709 AC XY: 52727 AN XY: 74338

African (AFR) AF: 0.838 AC: 34823 AN: 41534

American (AMR) AF: 0.704 AC: 10771 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2777 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2919 AN: 5110

South Asian (SAS) AF: 0.780 AC: 3768 AN: 4830

European-Finnish (FIN) AF: 0.535 AC: 5666 AN: 10584

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

European-Non Finnish (NFE) AF: 0.670 AC: 45503 AN: 67918

Other (OTH) AF: 0.747 AC: 1576 AN: 2110

Alfa AF: 0.689 Hom.: 4572

Bravo AF: 0.726

Asia WGS AF: 0.728 AC: 2528 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.41
PhyloP100		-1.1
PromoterAI		0.015	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3111873; hg19: chr2-96781986;