rs11195419

Positions:

• chr10-111079610-C-A

Variant summary

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

The NM_000681.4(ADRA2A):​c.*216C>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 0.138 in 619,010 control chromosomes in the GnomAD database, including 7,071 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 (2442 hom., cov: 33)
  • Exomes 𝑓: 0.13 (4629 hom.)
• Consequence: ADRA2A NM_000681.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA2A	NM_000681.4	c.*216C>A		3_prime_UTR_variant	1/1	ENST00000280155.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA2A	ENST00000280155.4	c.*216C>A		3_prime_UTR_variant	1/1		NM_000681.4	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24390 AN: 152108 Hom.: 2442 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.131 AC: 61147 AN: 466784 Hom.: 4629 Cov.: 4 AF XY: 0.133 AC XY: 32464 AN XY: 244716

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.0779

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.0943

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.160 AC: 24395 AN: 152226 Hom.: 2442 Cov.: 33 AF XY: 0.158 AC XY: 11735 AN XY: 74440

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.0992

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.142

Alfa AF: 0.123 Hom.: 1947

Bravo AF: 0.164

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.79

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: rs11195419; hg19: chr10-112839368; COSMIC: COSV54527147;