rs12676965

Positions:

• chr8-37823908-T-C

Variant summary

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

The NM_032777.10(ADGRA2):​c.339-4980T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,252 control chromosomes in the GnomAD database, including 2,038 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 0.15 (2038 hom., cov: 32)
• Consequence: ADGRA2 NM_032777.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA2	NM_032777.10	c.339-4980T>C		intron_variant		ENST00000412232.3	NP_116166.9
ADGRA2	XM_011544481.3	c.339-4980T>C		intron_variant			XP_011542783.1
ADGRA2	XM_011544482.3	c.267-4980T>C		intron_variant			XP_011542784.1
ADGRA2	XM_011544483.3	c.339-4980T>C		intron_variant			XP_011542785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA2	ENST00000412232.3	c.339-4980T>C		intron_variant		1	NM_032777.10	ENSP00000406367	P1
ADGRA2	ENST00000315215.11	c.339-4980T>C		intron_variant		1		ENSP00000323508
ADGRA2	ENST00000428068.5	c.213-4980T>C		intron_variant		3		ENSP00000400860

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22634 AN: 152134 Hom.: 2039 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.149 AC: 22627 AN: 152252 Hom.: 2038 Cov.: 32 AF XY: 0.147 AC XY: 10955 AN XY: 74432

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.172

Alfa AF: 0.188 Hom.: 3963

Bravo AF: 0.142

Asia WGS AF: 0.137 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.88

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: rs12676965; hg19: chr8-37681426;