Variant 8-37829952-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_032777.10(ADGRA2):c.656C>T(p.Ala219Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,609,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ADGRA2
NM_032777.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

ADGRA2 (HGNC:17849): (adhesion G protein-coupled receptor A2) Predicted to enable G protein-coupled receptor activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of Wnt signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ADGRA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34267834).

BS2

High AC in GnomAdExome4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADGRA2	NM_032777.10 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	6/19	ENST00000412232.3
ADGRA2	XM_011544481.3 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	6/19
ADGRA2	XM_011544482.3 linkuse as main transcript	c.584C>T	p.Ala195Val	missense_variant	5/18
ADGRA2	XM_011544483.3 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	6/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA2	ENST00000412232.3 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	6/19	1	NM_032777.10	P1	Q96PE1-1
ADGRA2	ENST00000315215.11 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	6/16	1			Q96PE1-2
ADGRA2	ENST00000428068.5 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000815

AC:

AN:

245446

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133378

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:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000288

AC:

AN:

1457650

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

725408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.656C>T (p.A219V) alteration is located in exon 6 (coding exon 6) of the ADGRA2 gene. This alteration results from a C to T substitution at nucleotide position 656, causing the alanine (A) at amino acid position 219 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

0.0051

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.078

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Uncertain

0.083

MutationTaster

Benign

0.68

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.43

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.87

T;T;T

Polyphen

0.18, 0.0020

.;B;B

Vest4

0.17, 0.13

MVP

0.67

MPC

0.28

ClinPred

0.34

GERP RS

5.2

Varity_R

0.093

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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