rs1800545

Positions:

• chr10-111077780-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000681.4(ADRA2A):​c.-217G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 498,550 control chromosomes in the GnomAD database, including 6,208 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 0.16 (2274 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3934 hom.)
• Consequence: ADRA2A NM_000681.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

Genes affected

ADRA2A (HGNC:281): (adrenoceptor alpha 2A) Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. The alpha-2-adrenergic receptors are a type of adrenergic receptors (for adrenaline or epinephrine), which inhibit adenylate cyclase. These receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from sympathetic nerves and from adrenergic neurons in the central nervous system. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Studies in mouse revealed that both the alpha2A and alpha2C receptor subtypes were required for presynaptic transmitter release from the sympathetic nervous system in the heart and from central noradrenergic neurons. The alpha-2-adrenergic receptors are also involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. A clear association between the alpha-2-adrenergic receptor and disease has not been yet established. [provided by RefSeq, Sep 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2A	NM_000681.4	c.-217G>A		5_prime_UTR_variant	1/1	ENST00000280155.4	NP_000672.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2A	ENST00000280155.4	c.-217G>A		5_prime_UTR_variant	1/1	6	NM_000681.4	ENSP00000280155.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23565 AN: 151376 Hom.: 2274 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0562

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.142 AC: 49432 AN: 347066 Hom.: 3934 Cov.: 6 AF XY: 0.141 AC XY: 24228 AN XY: 172422

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.0834

Gnomad4 ASJ exome AF: 0.0730

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.0919

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.156 AC: 23577 AN: 151484 Hom.: 2274 Cov.: 32 AF XY: 0.153 AC XY: 11350 AN XY: 74050

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0863

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.135

Alfa AF: 0.135 Hom.: 370

Bravo AF: 0.162

Asia WGS AF: 0.180 AC: 626 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.94

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: rs1800545; hg19: chr10-112837538;