Variant 8-37797512-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032777.10(ADGRA2):c.244C>A(p.Leu82Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,253,188 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: not found (cov: 33)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

ADGRA2
NM_032777.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35377824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA2	NM_032777.10 linkuse as main transcript	c.244C>A	p.Leu82Met	missense_variant	1/19	ENST00000412232.3	NP_116166.9	Q96PE1-1Q6YN44
ADGRA2	XM_011544481.3 linkuse as main transcript	c.244C>A	p.Leu82Met	missense_variant	1/19		XP_011542783.1
ADGRA2	XM_011544482.3 linkuse as main transcript	c.244C>A	p.Leu82Met	missense_variant	1/18		XP_011542784.1
ADGRA2	XM_011544483.3 linkuse as main transcript	c.244C>A	p.Leu82Met	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.244C>A	p.Leu82Met	missense_variant	1/19	1	NM_032777.10	ENSP00000406367.2	Q96PE1-1
ADGRA2	ENST00000315215.11 linkuse as main transcript	c.244C>A	p.Leu82Met	missense_variant	1/16	1		ENSP00000323508.7	Q96PE1-2
ADGRA2	ENST00000428068.5 linkuse as main transcript	c.140+13182C>A		intron_variant		3		ENSP00000400860.1	H7C1L1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

97382

Hom.:

AF XY:

0.0000182

AC XY:

AN XY:

54884

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:

0.0000414

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.98e-7

AC:

AN:

1253188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

613378

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:

9.92e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000178

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

Apr 20, 2023

The c.244C>A (p.L82M) 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 244, causing the leucine (L) at amino acid position 82 to be replaced by a methionine (M). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.43

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.098

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

1.0

D;D

Vest4

0.23

MutPred

0.22

Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);

MVP

0.45

MPC

0.93

ClinPred

0.67

GERP RS

3.7

Varity_R

0.38

gMVP

0.28

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