22-24429543-C-T

Position:

• chr22-24429543-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000675.6(ADORA2A):​c.-275+1797C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,240 control chromosomes in the GnomAD database, including 18,830 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 0.48 (18823 hom., cov: 34)
  • Exomes 𝑓: 0.63 (7 hom.)
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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]

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

SPECC1L-ADORA2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA2A	NM_000675.6	c.-275+1797C>T		intron_variant		ENST00000337539.12
ADORA2A-AS1	NR_028484.3	n.2494G>A		non_coding_transcript_exon_variant	7/7
SPECC1L-ADORA2A	NR_103546.1	n.3906-3588C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA2A	ENST00000337539.12	c.-275+1797C>T		intron_variant		1	NM_000675.6	P1
ADORA2A-AS1	ENST00000326341.8	n.2220G>A		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72632 AN: 152092 Hom.: 18813 Cov.: 34

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.633 AC: 19 AN: 30 Hom.: 7 Cov.: 0 AF XY: 0.583 AC XY: 14 AN XY: 24

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.477 AC: 72669 AN: 152210 Hom.: 18823 Cov.: 34 AF XY: 0.475 AC XY: 35339 AN XY: 74422

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.507

Alfa AF: 0.564 Hom.: 24906

Bravo AF: 0.476

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.41
DANN	Benign	0.59

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: rs2298383; hg19: chr22-24825511;