8-37829231-A-G

Variant names:

• chr8-37829231-A-G
• rs6468442
• NM_032777.10:c.411-30A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.95).
• 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 rank	MANE	Protein	UniProt
ADGRA2	NM_032777.10	c.411-30A>G		intron_variant	Intron 3 of 18	ENST00000412232.3	NP_116166.9
ADGRA2	XM_011544481.3	c.411-30A>G		intron_variant	Intron 3 of 18		XP_011542783.1
ADGRA2	XM_011544482.3	c.339-30A>G		intron_variant	Intron 2 of 17		XP_011542784.1
ADGRA2	XM_011544483.3	c.411-30A>G		intron_variant	Intron 3 of 17		XP_011542785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRA2	ENST00000412232.3	c.411-30A>G		intron_variant	Intron 3 of 18	1	NM_032777.10	ENSP00000406367.2
ADGRA2	ENST00000315215.11	c.411-30A>G		intron_variant	Intron 3 of 15	1		ENSP00000323508.7
ADGRA2	ENST00000428068.5	c.285-30A>G		intron_variant	Intron 3 of 5	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

GnomAD2 exomes AF: 0.812 AC: 203883 AN: 251066 AF XY: 0.804

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 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

African (AFR) AF: 0.950 AC: 31329 AN: 32970

American (AMR) AF: 0.840 AC: 37526 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 17782 AN: 25968

East Asian (EAS) AF: 0.868 AC: 34364 AN: 39578

South Asian (SAS) AF: 0.774 AC: 66347 AN: 85714

European-Finnish (FIN) AF: 0.851 AC: 45319 AN: 53244

Middle Eastern (MID) AF: 0.662 AC: 3786 AN: 5720

European-Non Finnish (NFE) AF: 0.791 AC: 860813 AN: 1087980

Other (OTH) AF: 0.790 AC: 46989 AN: 59466

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

African (AFR) AF: 0.946 AC: 38949 AN: 41170

American (AMR) AF: 0.805 AC: 12235 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2312 AN: 3462

East Asian (EAS) AF: 0.869 AC: 4400 AN: 5066

South Asian (SAS) AF: 0.791 AC: 3738 AN: 4728

European-Finnish (FIN) AF: 0.854 AC: 8956 AN: 10490

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 53851 AN: 67790

Other (OTH) AF: 0.806 AC: 1695 AN: 2102

Alfa AF: 0.803 Hom.: 214147

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
PhyloP100		-6.0
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs6468442; hg19: chr8-37686749;