Variant 2-96115207-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000682.7(ADRA2B):c.943G>A(p.Val315Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,562,968 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ADRA2B
NM_000682.7 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.834

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004224837).

BP6

Variant 2-96115207-C-T is Benign according to our data. Variant chr2-96115207-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 707706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2B	NM_000682.7 linkuse as main transcript	c.943G>A	p.Val315Met	missense_variant	1/1	ENST00000620793.2	NP_000673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793.2 linkuse as main transcript	c.943G>A	p.Val315Met	missense_variant	1/1		NM_000682.7	ENSP00000480573	P1

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

174

AN:

151466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000985

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000280

AC:

AN:

164484

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

87984

show subpopulations

Gnomad AFR exome

AF:

0.00324

Gnomad AMR exome

AF:

0.000633

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000433

GnomAD4 exome

AF:

0.000115

AC:

163

AN:

1411382

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

697512

show subpopulations

Gnomad4 AFR exome

AF:

0.00363

Gnomad4 AMR exome

AF:

0.000547

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.21e-7

Gnomad4 OTH exome

AF:

0.000444

GnomAD4 genome

AF:

0.00115

AC:

174

AN:

151586

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74068

show subpopulations

Gnomad4 AFR

AF:

0.00376

Gnomad4 AMR

AF:

0.000984

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000231

Hom.:

Bravo

AF:

0.00155

ESP6500AA

AF:

0.00286

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000217

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

2.5

DANN

Benign

0.88

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.84

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

Sift4G

Benign

0.28

Polyphen

0.030

Vest4

0.032

MVP

0.13

ClinPred

0.0045

GERP RS

-3.8

Varity_R

0.037

gMVP

0.18

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over