rs2236624

chr22-24440056-T-C

Variant summary

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

The NM_000675.6(ADORA2A):c.333-527T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 151,908 control chromosomes in the GnomAD database, including 49,342 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 0.80 (49342 hom., cov: 29)
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

ADORA2A (HGNC:263): (adenosine A2a receptor) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily, which is subdivided into classes and subtypes. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein, an adenosine receptor of A2A subtype, uses adenosine as the preferred endogenous agonist and preferentially interacts with the G(s) and G(olf) family of G proteins to increase intracellular cAMP levels. It plays an important role in many biological functions, such as cardiac rhythm and circulation, cerebral and renal blood flow, immune function, pain regulation, and sleep. It has been implicated in pathophysiological conditions such as inflammatory diseases and neurodegenerative disorders. Alternative splicing results in multiple transcript variants. A read-through transcript composed of the upstream SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding. [provided by RefSeq, Jun 2013]

ADORA2A-AS1 (HGNC:37122): (ADORA2A antisense RNA 1)

SPECC1L-ADORA2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA2A	NM_000675.6	c.333-527T>C		intron_variant		ENST00000337539.12
ADORA2A-AS1	NR_028484.3	n.833+1936A>G		intron_variant, non_coding_transcript_variant
SPECC1L-ADORA2A	NR_103546.1	n.4512-527T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA2A	ENST00000337539.12	c.333-527T>C		intron_variant		1	NM_000675.6	P1
ADORA2A-AS1	ENST00000326341.8	n.559+1936A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121354 AN: 151790 Hom.: 49280 Cov.: 29

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.800 AC: 121483 AN: 151908 Hom.: 49342 Cov.: 29 AF XY: 0.794 AC XY: 58913 AN XY: 74226

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.796

Alfa AF: 0.757 Hom.: 59189

Bravo AF: 0.820

Asia WGS AF: 0.719 AC: 2498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.26
Dann	Benign	0.58

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: rs2236624; hg19: chr22-24836024;