22-24433800-G-C

Variant names:

• chr22-24433800-G-C
• rs13306116
• NM_000675.6:c.332+64G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000675.6(ADORA2A):​c.332+64G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,362,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000675.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA2A	NM_000675.6	MANE Select	c.332+64G>C		intron	N/A	NP_000666.2
	ADORA2A	NM_001278497.2		c.332+64G>C		intron	N/A	NP_001265426.1
	ADORA2A	NM_001278498.2		c.332+64G>C		intron	N/A	NP_001265427.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA2A	ENST00000337539.12	TSL:1 MANE Select	c.332+64G>C		intron	N/A	ENSP00000336630.6
	ADORA2A	ENST00000618076.3	TSL:1	c.332+64G>C		intron	N/A	ENSP00000481552.1
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*1467+64G>C		intron	N/A	ENSP00000351480.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000661 AC: 9 AN: 1362118 Hom.: 0 AF XY: 0.00000446 AC XY: 3 AN XY: 672192

African (AFR) AF: 0.00 AC: 0 AN: 31902

American (AMR) AF: 0.00 AC: 0 AN: 39698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22672

East Asian (EAS) AF: 0.00 AC: 0 AN: 38288

South Asian (SAS) AF: 0.00 AC: 0 AN: 76934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.00000854 AC: 9 AN: 1053858

Other (OTH) AF: 0.00 AC: 0 AN: 56924

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.071
DANN	Benign	0.47
PhyloP100		-1.3

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

Other links and lift over

dbSNP: rs13306116; hg19: chr22-24829768;