rs2779212

Positions:

• chr17-15973341-T-C
• chr17-15973341-T-G

Variant summary

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

The NM_000676.4(ADORA2B):​c.336-1338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,132 control chromosomes in the GnomAD database, including 27,941 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 0.60 (27941 hom., cov: 32)
• Consequence: ADORA2B NM_000676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

Genes affected

ADORA2B (HGNC:264): (adenosine A2b receptor) This gene encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. The gene is located near the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA2B	NM_000676.4	c.336-1338T>C		intron_variant		ENST00000304222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA2B	ENST00000304222.3	c.336-1338T>C		intron_variant		1	NM_000676.4	P1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91123 AN: 152014 Hom.: 27890 Cov.: 32

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.600 AC: 91242 AN: 152132 Hom.: 27941 Cov.: 32 AF XY: 0.598 AC XY: 44455 AN XY: 74364

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.591

Alfa AF: 0.497 Hom.: 2232

Bravo AF: 0.597

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.45

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: rs2779212; hg19: chr17-15876655; COSMIC: COSV58483412; COSMIC: COSV58483412;