Variant 8-37830746-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_032777.10(ADGRA2):c.755C>A(p.Pro252Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,453,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ADGRA2
NM_032777.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADGRA2	NM_032777.10 linkuse as main transcript	c.755C>A	p.Pro252Gln	missense_variant	7/19	ENST00000412232.3
ADGRA2	XM_011544481.3 linkuse as main transcript	c.755C>A	p.Pro252Gln	missense_variant	7/19
ADGRA2	XM_011544482.3 linkuse as main transcript	c.683C>A	p.Pro228Gln	missense_variant	6/18
ADGRA2	XM_011544483.3 linkuse as main transcript	c.755C>A	p.Pro252Gln	missense_variant	7/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA2	ENST00000412232.3 linkuse as main transcript	c.755C>A	p.Pro252Gln	missense_variant	7/19	1	NM_032777.10	P1	Q96PE1-1
ADGRA2	ENST00000315215.11 linkuse as main transcript	c.755C>A	p.Pro252Gln	missense_variant	7/16	1			Q96PE1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000852

AC:

AN:

234702

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127030

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000571

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000949

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1453536

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Sep 17, 2021

The c.755C>A (p.P252Q) alteration is located in exon 7 (coding exon 7) of the ADGRA2 gene. This alteration results from a C to A substitution at nucleotide position 755, causing the proline (P) at amino acid position 252 to be replaced by a glutamine (Q). 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

0.99

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Uncertain

-0.15

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.76

MutPred

0.50

Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);

MVP

0.70

MPC

0.92

ClinPred

0.98

GERP RS

5.2

Varity_R

0.63

gMVP

0.55

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