chr22-24439072-C-CTTTTTTTTTT

Variant names:

• chr22-24439072-C-CTTTTTTTTTT
• rs3032740
• NM_000675.6:c.333-1491_333-1482dupTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000675.6(ADORA2A):​c.333-1491_333-1482dupTTTTTTTTTT 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 0.0047 (59 hom., cov: 20)
  • Failed GnomAD Quality Control
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.333-1491_333-1482dupTTTTTTTTTT		intron	N/A	NP_000666.2
	ADORA2A	NM_001278497.2		c.333-1491_333-1482dupTTTTTTTTTT		intron	N/A	NP_001265426.1	P29274
	ADORA2A	NM_001278498.2		c.333-1491_333-1482dupTTTTTTTTTT		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_333-1510insTTTTTTTTTT		intron	N/A	ENSP00000336630.6	P29274
	ADORA2A	ENST00000618076.3	TSL:1	c.333-1511_333-1510insTTTTTTTTTT		intron	N/A	ENSP00000481552.1	P29274
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*1468-1511_*1468-1510insTTTTTTTTTT		intron	N/A	ENSP00000351480.2	F8WAN1

Frequencies

GnomAD3 genomes AF: 0.00471 AC: 344 AN: 73084 Hom.: 59 Cov.: 20

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00183

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00471

Gnomad SAS AF: 0.000674

Gnomad FIN AF: 0.000560

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00625

Gnomad OTH AF: 0.00662

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00471 AC: 344 AN: 73092 Hom.: 59 Cov.: 20 AF XY: 0.00468 AC XY: 153 AN XY: 32698

African (AFR) AF: 0.00176 AC: 39 AN: 22184

American (AMR) AF: 0.00359 AC: 18 AN: 5010

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 37 AN: 2102

East Asian (EAS) AF: 0.00473 AC: 8 AN: 1690

South Asian (SAS) AF: 0.000677 AC: 1 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: 0.00625 AC: 233 AN: 37272

Other (OTH) AF: 0.00659 AC: 6 AN: 910

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;