rs13306116

Positions:

• chr22-24433800-G-A
• chr22-24433800-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000675.6(ADORA2A):​c.332+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,514,468 control chromosomes in the GnomAD database, including 14 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 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (14 hom.)
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.87).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00183 (279/152358) while in subpopulation EAS AF= 0.0199 (103/5178). AF 95% confidence interval is 0.0168. There are 0 homozygotes in gnomad4. There are 158 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 279 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA2A	NM_000675.6	c.332+64G>A		intron_variant		ENST00000337539.12
ADORA2A-AS1	NR_028484.3	n.834-1366C>T		intron_variant, non_coding_transcript_variant
SPECC1L-ADORA2A	NR_103546.1	n.4511+64G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA2A	ENST00000337539.12	c.332+64G>A		intron_variant		1	NM_000675.6	P1
ADORA2A-AS1	ENST00000326341.8	n.560-1366C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 279 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00181 AC: 2466 AN: 1362110 Hom.: 14 AF XY: 0.00172 AC XY: 1159 AN XY: 672188

Gnomad4 AFR exome AF: 0.000690

Gnomad4 AMR exome AF: 0.000504

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0207

Gnomad4 SAS exome AF: 0.000767

Gnomad4 FIN exome AF: 0.0000550

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.00346

GnomAD4 genome AF: 0.00183 AC: 279 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.00212 AC XY: 158 AN XY: 74500

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.00226

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.57

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: rs13306116; hg19: chr22-24829768; COSMIC: COSV58378488; COSMIC: COSV58378488;