Variant 8-37797446-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032777.10(ADGRA2):c.178G>A(p.Gly60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000998 in 1,413,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

ADGRA2
NM_032777.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.747

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0120592415).

BS2

High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA2	NM_032777.10 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	1/19	ENST00000412232.3	NP_116166.9	Q96PE1-1Q6YN44
ADGRA2	XM_011544481.3 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	1/19		XP_011542783.1
ADGRA2	XM_011544482.3 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	1/18		XP_011542784.1
ADGRA2	XM_011544483.3 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	1/18		XP_011542785.1	D3DSW5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRA2	ENST00000412232.3 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	1/19	1	NM_032777.10	ENSP00000406367.2	Q96PE1-1
ADGRA2	ENST00000315215.11 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	1/16	1		ENSP00000323508.7	Q96PE1-2
ADGRA2	ENST00000428068.5 linkuse as main transcript	c.140+13116G>A		intron_variant		3		ENSP00000400860.1	H7C1L1

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000761

AC:

AN:

1260946

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

617396

show subpopulations

Gnomad4 AFR exome

AF:

0.000823

Gnomad4 AMR exome

AF:

0.0000604

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:

0.0000670

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.000296

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000249

ExAC

AF:

0.0000460

AC:

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.178G>A (p.G60S) alteration is located in exon 1 (coding exon 1) of the ADGRA2 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the glycine (G) at amino acid position 60 to be replaced by a serine (S). 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

0.065

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.57

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.037

Sift

Benign

0.35

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.39

B;B

Vest4

0.10

MutPred

0.18

Gain of phosphorylation at G60 (P = 0.0177);Gain of phosphorylation at G60 (P = 0.0177);

MVP

0.048

MPC

0.27

ClinPred

0.020

GERP RS

3.6

Varity_R

0.046

gMVP

0.22

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