22-24429543-C-T

Variant names:

• chr22-24429543-C-T
• rs2298383
• NM_000675.6:c.-275+1797C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 88 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADORA2A	NM_000675.6	c.-275+1797C>T		intron_variant	Intron 1 of 2	ENST00000337539.12	NP_000666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADORA2A	ENST00000337539.12	c.-275+1797C>T		intron_variant	Intron 1 of 2	1	NM_000675.6	ENSP00000336630.6
SPECC1L-ADORA2A	ENST00000358654.2	n.*862-3588C>T		intron_variant	Intron 18 of 19	2		ENSP00000351480.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.708 AC: 17 AN: 24

Other (OTH) AF: 0.333 AC: 2 AN: 6

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

African (AFR) AF: 0.275 AC: 11421 AN: 41536

American (AMR) AF: 0.526 AC: 8047 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1944 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2533 AN: 5170

South Asian (SAS) AF: 0.319 AC: 1542 AN: 4832

European-Finnish (FIN) AF: 0.550 AC: 5821 AN: 10590

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.582 AC: 39600 AN: 67994

Other (OTH) AF: 0.507 AC: 1073 AN: 2116

Alfa AF: 0.560 Hom.: 34743

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
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2298383; hg19: chr22-24825511;