chr22-24438763-A-G

Variant names:

• chr22-24438763-A-G
• rs9624472
• NM_000675.6:c.333-1820A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000675.6(ADORA2A):​c.333-1820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 152,260 control chromosomes in the GnomAD database, including 845 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 0.098 (845 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 10 publications found

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]

SPECC1L-ADORA2A (HGNC:49185): (SPECC1L-ADORA2A readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) genes on chromosome 22. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jun 2013]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000675.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA2A	NM_000675.6	MANE Select	c.333-1820A>G		intron	N/A	NP_000666.2
	ADORA2A	NM_001278497.2		c.333-1820A>G		intron	N/A	NP_001265426.1	P29274
	ADORA2A	NM_001278498.2		c.333-1820A>G		intron	N/A	NP_001265427.1	X5DNB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA2A	ENST00000337539.12	TSL:1 MANE Select	c.333-1820A>G		intron	N/A	ENSP00000336630.6	P29274
	ADORA2A	ENST00000618076.3	TSL:1	c.333-1820A>G		intron	N/A	ENSP00000481552.1	P29274
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*1468-1820A>G		intron	N/A	ENSP00000351480.2	F8WAN1

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14917 AN: 152142 Hom.: 844 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0952

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0981 AC: 14940 AN: 152260 Hom.: 845 Cov.: 32 AF XY: 0.0951 AC XY: 7078 AN XY: 74440

African (AFR) AF: 0.146 AC: 6083 AN: 41530

American (AMR) AF: 0.0636 AC: 974 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4828

European-Finnish (FIN) AF: 0.0750 AC: 795 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0895 AC: 6090 AN: 68018

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.0944 Hom.: 105

Bravo AF: 0.101

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9624472; hg19: chr22-24834731;