8-37800008-G-A

Variant names:

• chr8-37800008-G-A
• rs915650
• NM_032777.10:c.266+2474G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032777.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA2	NM_032777.10	MANE Select	c.266+2474G>A		intron	N/A	NP_116166.9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA2	ENST00000412232.3	TSL:1 MANE Select	c.266+2474G>A		intron	N/A	ENSP00000406367.2
	ADGRA2	ENST00000315215.11	TSL:1	c.266+2474G>A		intron	N/A	ENSP00000323508.7
	ADGRA2	ENST00000428068.5	TSL:3	c.141-14888G>A		intron	N/A	ENSP00000400860.1

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

African (AFR) AF: 0.362 AC: 15007 AN: 41410

American (AMR) AF: 0.354 AC: 5396 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2286 AN: 5144

South Asian (SAS) AF: 0.344 AC: 1655 AN: 4810

European-Finnish (FIN) AF: 0.344 AC: 3635 AN: 10566

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25413 AN: 67954

Other (OTH) AF: 0.368 AC: 775 AN: 2104

Alfa AF: 0.376 Hom.: 15699

Bravo AF: 0.370

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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