rs915650

chr8-37800008-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032777.10(ADGRA2):c.266+2474G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,924 control chromosomes in the GnomAD database, including 10,416 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10416 hom., cov: 32)
• Consequence: ADGRA2 NM_032777.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRA2	NM_032777.10	c.266+2474G>A		intron_variant		ENST00000412232.3
ADGRA2	XM_011544481.3	c.266+2474G>A		intron_variant
ADGRA2	XM_011544482.3	c.266+2474G>A		intron_variant
ADGRA2	XM_011544483.3	c.266+2474G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA2	ENST00000412232.3	c.266+2474G>A		intron_variant		1	NM_032777.10	P1
ADGRA2	ENST00000315215.11	c.266+2474G>A		intron_variant		1
ADGRA2	ENST00000428068.5	c.141-14888G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56034 AN: 151806 Hom.: 10413 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.369 AC: 56043 AN: 151924 Hom.: 10416 Cov.: 32 AF XY: 0.368 AC XY: 27339 AN XY: 74244

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.368

Alfa AF: 0.377 Hom.: 10681

Bravo AF: 0.370

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.9
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs915650; hg19: chr8-37657526; COSMIC: COSV59447625;