22-24439072-C-CTTTTTTTTTTTTT

Position:

• chr22-24439072-C-CTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000675.6(ADORA2A):​c.333-1494_333-1482dup variant causes a intron 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 0.00048 (6 hom., cov: 20)
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA2A	NM_000675.6	c.333-1494_333-1482dup		intron_variant		ENST00000337539.12	NP_000666.2
ADORA2A-AS1	NR_028484.3	n.833+2919_833+2920insAAAAAAAAAAAAA		intron_variant, non_coding_transcript_variant
SPECC1L-ADORA2A	NR_103546.1	n.4512-1494_4512-1482dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA2A	ENST00000337539.12	c.333-1494_333-1482dup		intron_variant		1	NM_000675.6	ENSP00000336630	P1
ADORA2A-AS1	ENST00000326341.8	n.559+2919_559+2920insAAAAAAAAAAAAA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000479 AC: 35 AN: 73094 Hom.: 6 Cov.: 20

Gnomad AFR AF: 0.000180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000400

Gnomad ASJ AF: 0.000476

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000674

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000671

Gnomad OTH AF: 0.00221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000479 AC: 35 AN: 73102 Hom.: 6 Cov.: 20 AF XY: 0.000245 AC XY: 8 AN XY: 32702

Gnomad4 AFR AF: 0.000180

Gnomad4 AMR AF: 0.000399

Gnomad4 ASJ AF: 0.000476

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000677

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000671

Gnomad4 OTH AF: 0.00220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3032740; hg19: chr22-24835040;