Variant 8-37828896-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032777.10(ADGRA2):c.347G>C(p.Arg116Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,600,134 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ADGRA2
NM_032777.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADGRA2	NM_032777.10 linkuse as main transcript	c.347G>C	p.Arg116Thr	missense_variant	3/19	ENST00000412232.3
ADGRA2	XM_011544481.3 linkuse as main transcript	c.347G>C	p.Arg116Thr	missense_variant	3/19
ADGRA2	XM_011544482.3 linkuse as main transcript	c.275G>C	p.Arg92Thr	missense_variant	2/18
ADGRA2	XM_011544483.3 linkuse as main transcript	c.347G>C	p.Arg116Thr	missense_variant	3/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA2	ENST00000412232.3 linkuse as main transcript	c.347G>C	p.Arg116Thr	missense_variant	3/19	1	NM_032777.10	P1	Q96PE1-1
ADGRA2	ENST00000315215.11 linkuse as main transcript	c.347G>C	p.Arg116Thr	missense_variant	3/16	1			Q96PE1-2
ADGRA2	ENST00000428068.5 linkuse as main transcript	c.221G>C	p.Arg74Thr	missense_variant	3/6	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152036

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

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1448098

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719684

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74250

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:

0.00000378

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

Jun 17, 2022

The c.347G>C (p.R116T) alteration is located in exon 3 (coding exon 3) of the ADGRA2 gene. This alteration results from a G to C substitution at nucleotide position 347, causing the arginine (R) at amino acid position 116 to be replaced by a threonine (T). 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

0.070

Eigen_PC

Benign

0.094

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

T;T;D

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.019

D;D;D

Sift4G

Benign

0.29

T;D;D

Polyphen

0.98, 0.68

.;D;P

Vest4

0.59, 0.61

MutPred

0.59

.;Loss of stability (P = 0.0879);Loss of stability (P = 0.0879);

MVP

0.54

MPC

0.74

ClinPred

0.94

GERP RS

3.7

Varity_R

0.36

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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