Variant 8-37797308-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032777.10(ADGRA2):c.40C>A(p.Arg14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADGRA2
NM_032777.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.209

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.136951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADGRA2	NM_032777.10 linkuse as main transcript	c.40C>A	p.Arg14Ser	missense_variant	1/19	ENST00000412232.3
ADGRA2	XM_011544481.3 linkuse as main transcript	c.40C>A	p.Arg14Ser	missense_variant	1/19
ADGRA2	XM_011544482.3 linkuse as main transcript	c.40C>A	p.Arg14Ser	missense_variant	1/18
ADGRA2	XM_011544483.3 linkuse as main transcript	c.40C>A	p.Arg14Ser	missense_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA2	ENST00000412232.3 linkuse as main transcript	c.40C>A	p.Arg14Ser	missense_variant	1/19	1	NM_032777.10	P1	Q96PE1-1
ADGRA2	ENST00000315215.11 linkuse as main transcript	c.40C>A	p.Arg14Ser	missense_variant	1/16	1			Q96PE1-2
ADGRA2	ENST00000428068.5 linkuse as main transcript	c.140+12978C>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1168006

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

565646

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 14, 2022

The c.40C>A (p.R14S) alteration is located in exon 1 (coding exon 1) of the ADGRA2 gene. This alteration results from a C to A substitution at nucleotide position 40, causing the arginine (R) at amino acid position 14 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

0.23

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.59

T;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.062

Sift

Benign

0.098

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0080

B;B

Vest4

0.25

MutPred

0.42

Loss of methylation at R14 (P = 0.0022);Loss of methylation at R14 (P = 0.0022);

MVP

0.25

MPC

0.31

ClinPred

0.13

GERP RS

2.1

Varity_R

0.16

gMVP

0.50

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over