2-96114374-G-T

Variant names:

• chr2-96114374-G-T
• rs4907299
• NM_000682.7:c.*423C>A

Variant summary

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

The NM_000682.7(ADRA2B):​c.*423C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 998,272 control chromosomes in the GnomAD database, including 50,897 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 0.32 (8318 hom., cov: 33)
  • Exomes 𝑓: 0.32 (42579 hom.)
• Consequence: ADRA2B NM_000682.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 19 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 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.*423C>A		3_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.*423C>A		3_prime_UTR	Exon 1 of 1	ENSP00000480573.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48412 AN: 151956 Hom.: 8299 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.315 AC: 266917 AN: 846198 Hom.: 42579 Cov.: 28 AF XY: 0.314 AC XY: 122875 AN XY: 391436

African (AFR) AF: 0.248 AC: 3963 AN: 15994

American (AMR) AF: 0.489 AC: 1617 AN: 3308

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 898 AN: 5352

East Asian (EAS) AF: 0.475 AC: 1986 AN: 4180

South Asian (SAS) AF: 0.196 AC: 3528 AN: 17958

European-Finnish (FIN) AF: 0.426 AC: 212 AN: 498

Middle Eastern (MID) AF: 0.125 AC: 207 AN: 1654

European-Non Finnish (NFE) AF: 0.320 AC: 246569 AN: 769336

Other (OTH) AF: 0.284 AC: 7937 AN: 27918

GnomAD4 genome AF: 0.319 AC: 48482 AN: 152074 Hom.: 8318 Cov.: 33 AF XY: 0.325 AC XY: 24137 AN XY: 74338

African (AFR) AF: 0.261 AC: 10838 AN: 41482

American (AMR) AF: 0.398 AC: 6074 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2542 AN: 5154

South Asian (SAS) AF: 0.202 AC: 974 AN: 4824

European-Finnish (FIN) AF: 0.471 AC: 4981 AN: 10576

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21448 AN: 67978

Other (OTH) AF: 0.276 AC: 583 AN: 2114

Alfa AF: 0.292 Hom.: 4514

Bravo AF: 0.322

Asia WGS AF: 0.311 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4907299; hg19: chr2-96780122;