8-37829231-A-G

Position:

• chr8-37829231-A-G

Variant summary

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

The NM_032777.10(ADGRA2):​c.411-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,586,536 control chromosomes in the GnomAD database, including 511,766 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 0.84 (53981 hom., cov: 26)
  • Exomes 𝑓: 0.80 (457785 hom.)
• Consequence: ADGRA2 NM_032777.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.98

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA2	NM_032777.10	c.411-30A>G		intron_variant		ENST00000412232.3	NP_116166.9
ADGRA2	XM_011544481.3	c.411-30A>G		intron_variant			XP_011542783.1
ADGRA2	XM_011544482.3	c.339-30A>G		intron_variant			XP_011542784.1
ADGRA2	XM_011544483.3	c.411-30A>G		intron_variant			XP_011542785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA2	ENST00000412232.3	c.411-30A>G		intron_variant		1	NM_032777.10	ENSP00000406367.2
ADGRA2	ENST00000315215.11	c.411-30A>G		intron_variant		1		ENSP00000323508.7
ADGRA2	ENST00000428068.5	c.285-30A>G		intron_variant		3		ENSP00000400860.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127040 AN: 151084 Hom.: 53922 Cov.: 26

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.806

GnomAD3 exomes AF: 0.812 AC: 203883 AN: 251066 Hom.: 83347 AF XY: 0.804 AC XY: 109126 AN XY: 135704

Gnomad AFR exome AF: 0.947

Gnomad AMR exome AF: 0.845

Gnomad ASJ exome AF: 0.679

Gnomad EAS exome AF: 0.862

Gnomad SAS exome AF: 0.775

Gnomad FIN exome AF: 0.853

Gnomad NFE exome AF: 0.789

Gnomad OTH exome AF: 0.796

GnomAD4 exome AF: 0.797 AC: 1144255 AN: 1435332 Hom.: 457785 Cov.: 27 AF XY: 0.796 AC XY: 569859 AN XY: 715810

Gnomad4 AFR exome AF: 0.950

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.685

Gnomad4 EAS exome AF: 0.868

Gnomad4 SAS exome AF: 0.774

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.790

GnomAD4 genome AF: 0.841 AC: 127160 AN: 151204 Hom.: 53981 Cov.: 26 AF XY: 0.842 AC XY: 62101 AN XY: 73782

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.806

Alfa AF: 0.789 Hom.: 101124

Bravo AF: 0.846

Asia WGS AF: 0.824 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0040
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6468442; hg19: chr8-37686749;