Variant 10-111078799-TGGGCCCCGAGCGCAGCGC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM4BP6_ModerateBS2_Supporting

The NM_000681.4(ADRA2A):c.810_827del(p.Glu271_Pro276del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00453 in 1,300,918 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 18 hom. )

Consequence

ADRA2A
NM_000681.4 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.03

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 Likely_benign. Variant got -1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000681.4.

BP6

Variant 10-111078799-TGGGCCCCGAGCGCAGCGC-T is Benign according to our data. Variant chr10-111078799-TGGGCCCCGAGCGCAGCGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1338705.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA2A	NM_000681.4 linkuse as main transcript	c.810_827del	p.Glu271_Pro276del	inframe_deletion	1/1	ENST00000280155.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA2A	ENST00000280155.4 linkuse as main transcript	c.810_827del	p.Glu271_Pro276del	inframe_deletion	1/1		NM_000681.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00372

AC:

559

AN:

150236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000704

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000797

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00565

Gnomad OTH

AF:

0.000972

GnomAD3 exomes

AF:

0.00814

AC:

103

AN:

12648

Hom.:

AF XY:

0.00736

AC XY:

AN XY:

6524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.00340

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00464

AC:

5339

AN:

1150576

Hom.:

AF XY:

0.00446

AC XY:

2474

AN XY:

554148

show subpopulations

Gnomad4 AFR exome

AF:

0.000664

Gnomad4 AMR exome

AF:

0.000117

Gnomad4 ASJ exome

AF:

0.0000687

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000283

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.00495

Gnomad4 OTH exome

AF:

0.00296

GnomAD4 genome

AF:

0.00372

AC:

559

AN:

150342

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

282

AN XY:

73448

show subpopulations

Gnomad4 AFR

AF:

0.000702

Gnomad4 AMR

AF:

0.000796

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.00565

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.00513

Hom.:

Bravo

AF:

0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 12, 2021

- -

ADRA2A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over