chr22-24439072-C-CTT

Variant names:

• chr22-24439072-C-CTT
• rs3032740
• NM_000675.6:c.333-1483_333-1482dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000675.6(ADORA2A):​c.333-1483_333-1482dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0067 (79 hom., cov: 20)
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 11 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 492 AD gene.

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.333-1483_333-1482dupTT		intron	N/A	NP_000666.2
	ADORA2A	NM_001278497.2		c.333-1483_333-1482dupTT		intron	N/A	NP_001265426.1	P29274
	ADORA2A	NM_001278498.2		c.333-1483_333-1482dupTT		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.333-1511_333-1510insTT		intron	N/A	ENSP00000336630.6	P29274
	ADORA2A	ENST00000618076.3	TSL:1	c.333-1511_333-1510insTT		intron	N/A	ENSP00000481552.1	P29274
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*1468-1511_*1468-1510insTT		intron	N/A	ENSP00000351480.2	F8WAN1

Frequencies

GnomAD3 genomes AF: 0.00673 AC: 492 AN: 73056 Hom.: 79 Cov.: 20

Gnomad AFR AF: 0.00682

Gnomad AMI AF: 0.00183

Gnomad AMR AF: 0.00480

Gnomad ASJ AF: 0.0195

Gnomad EAS AF: 0.00236

Gnomad SAS AF: 0.00202

Gnomad FIN AF: 0.000560

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00692

Gnomad OTH AF: 0.00998

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

GnomAD4 genome AF: 0.00673 AC: 492 AN: 73064 Hom.: 79 Cov.: 20 AF XY: 0.00483 AC XY: 158 AN XY: 32686

African (AFR) AF: 0.00681 AC: 151 AN: 22174

American (AMR) AF: 0.00479 AC: 24 AN: 5010

Ashkenazi Jewish (ASJ) AF: 0.0195 AC: 41 AN: 2098

East Asian (EAS) AF: 0.00237 AC: 4 AN: 1690

South Asian (SAS) AF: 0.00203 AC: 3 AN: 1478

European-Finnish (FIN) AF: 0.000560 AC: 1 AN: 1786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 114

European-Non Finnish (NFE) AF: 0.00692 AC: 258 AN: 37262

Other (OTH) AF: 0.00993 AC: 9 AN: 906

Alfa AF: 0.00 Hom.: 98

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.052

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3032740; hg19: chr22-24835040;