Variant 10-111079134-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_000681.4(ADRA2A):c.1138C>A(p.Arg380Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,602,504 control chromosomes in the GnomAD database, including 4,179 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 0.053 ( 610 hom., cov: 33)

Exomes 𝑓: 0.026 ( 3569 hom. )

Consequence

ADRA2A
NM_000681.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.374

Variant links:

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]

ADRA2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=0.374 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2A	NM_000681.4 linkuse as main transcript	c.1138C>A	p.Arg380Arg	synonymous_variant	1/1	ENST00000280155.4	NP_000672.3	P08913

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2A	ENST00000280155.4 linkuse as main transcript	c.1138C>A	p.Arg380Arg	synonymous_variant	1/1	6	NM_000681.4	ENSP00000280155.2		P08913

Frequencies

GnomAD3 genomes

AF:

0.0528

AC:

8033

AN:

152024

Hom.:

601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0752

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.0751

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00540

Gnomad OTH

AF:

0.0547

GnomAD3 exomes

AF:

0.0738

AC:

17900

AN:

242440

Hom.:

1990

AF XY:

0.0654

AC XY:

8607

AN XY:

131592

show subpopulations

Gnomad AFR exome

AF:

0.0797

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.00186

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.0697

Gnomad FIN exome

AF:

0.0176

Gnomad NFE exome

AF:

0.00581

Gnomad OTH exome

AF:

0.0432

GnomAD4 exome

AF:

0.0263

AC:

38074

AN:

1450366

Hom.:

3569

Cov.:

AF XY:

0.0262

AC XY:

18841

AN XY:

720282

show subpopulations

Gnomad4 AFR exome

AF:

0.0779

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.00109

Gnomad4 EAS exome

AF:

0.302

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.0152

Gnomad4 NFE exome

AF:

0.00464

Gnomad4 OTH exome

AF:

0.0402

GnomAD4 genome

AF:

0.0530

AC:

8065

AN:

152138

Hom.:

610

Cov.:

AF XY:

0.0580

AC XY:

4315

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0752

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.0753

Gnomad4 FIN

AF:

0.0170

Gnomad4 NFE

AF:

0.00540

Gnomad4 OTH

AF:

0.0546

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0650

Asia WGS

AF:

0.179

AC:

619

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.8

DANN

Benign

0.96

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over