22-24441941-C-CT

Position:

• chr22-24441941-C-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000675.6(ADORA2A):​c.*458dup variant causes a 3 prime UTR 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 0.52 (21576 hom., cov: 0)
  • Exomes 𝑓: 0.47 (613 hom.)
• Consequence: ADORA2A NM_000675.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

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:):

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA2A	NM_000675.6	c.*458dup		3_prime_UTR_variant	3/3	ENST00000337539.12
SPECC1L-ADORA2A	NR_103546.1	n.5876dup		non_coding_transcript_exon_variant	20/20
ADORA2A-AS1	NR_028484.3	n.833+50_833+51insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA2A	ENST00000337539.12	c.*458dup		3_prime_UTR_variant	3/3	1	NM_000675.6	P1
ADORA2A-AS1	ENST00000326341.8	n.559+50_559+51insA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78968 AN: 152006 Hom.: 21559 Cov.: 0

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.543

GnomAD4 exome AF: 0.475 AC: 2155 AN: 4538 Hom.: 613 Cov.: 0 AF XY: 0.483 AC XY: 1149 AN XY: 2378

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.468

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.520 AC: 79035 AN: 152124 Hom.: 21576 Cov.: 0 AF XY: 0.516 AC XY: 38361 AN XY: 74372

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.544

Alfa AF: 0.559 Hom.: 2949

Bravo AF: 0.517

Asia WGS AF: 0.404 AC: 1407 AN: 3478

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: rs35060421; hg19: chr22-24837909;