chr22-24439072-C-CT

Position:

• chr22-24439072-C-CT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000675.6(ADORA2A):​c.333-1482dupT 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 0.020 (247 hom., cov: 20)
  • Failed GnomAD Quality Control
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA2A	NM_000675.6	c.333-1482dupT		intron_variant		ENST00000337539.12	NP_000666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA2A	ENST00000337539.12	c.333-1482dupT		intron_variant		1	NM_000675.6	ENSP00000336630.6
SPECC1L-ADORA2A	ENST00000358654.2	n.*1468-1482dupT		intron_variant		2		ENSP00000351480.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1453 AN: 72972 Hom.: 247 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0293

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.0195

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.00876

Gnomad FIN AF: 0.00786

Gnomad MID AF: 0.00806

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0188

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: 0.0199 AC: 1453 AN: 72980 Hom.: 247 Cov.: 20 AF XY: 0.0188 AC XY: 614 AN XY: 32654

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.0195

Gnomad4 EAS AF: 0.0428

Gnomad4 SAS AF: 0.00880

Gnomad4 FIN AF: 0.00786

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3032740; hg19: chr22-24835040;