22-24441941-C-CT

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000675.6(ADORA2A):c.*458dupT variant causes a 3 prime UTR 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 0.52 ( 21576 hom., cov: 0)

Exomes 𝑓: 0.47 ( 613 hom. )

Consequence

ADORA2A
NM_000675.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.657

Publications

6 publications found

Variant links:

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 links:

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]

SPECC1L-ADORA2A links:

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

ADORA2A-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADORA2A	NM_000675.6	MANE Select	c.*458dupT	3_prime_UTR	Exon 3 of 3	NP_000666.2
ADORA2A	NM_001278497.2		c.*458dupT	3_prime_UTR	Exon 4 of 4	NP_001265426.1	P29274
ADORA2A	NM_001278498.2		c.*458dupT	3_prime_UTR	Exon 3 of 3	NP_001265427.1	X5DNB4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADORA2A	ENST00000337539.12	TSL:1 MANE Select	c.*458dupT	3_prime_UTR	Exon 3 of 3	ENSP00000336630.6	P29274
ADORA2A	ENST00000618076.3	TSL:1	c.*458dupT	3_prime_UTR	Exon 3 of 3	ENSP00000481552.1	P29274
SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*2832dupT	non_coding_transcript_exon	Exon 20 of 20	ENSP00000351480.2	F8WAN1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78968

AN:

152006

Hom.:

21559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.493

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.608

Gnomad OTH

AF:

0.543

GnomAD4 exome

AF:

0.475

AC:

2155

AN:

4538

Hom.:

613

Cov.:

AF XY:

0.483

AC XY:

1149

AN XY:

2378

show subpopulations

African (AFR)

AF:

0.284

AC:

AN:

218

American (AMR)

AF:

0.448

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

180

East Asian (EAS)

AF:

0.468

AC:

116

AN:

248

South Asian (SAS)

AF:

0.258

AC:

AN:

European-Finnish (FIN)

AF:

0.522

AC:

308

AN:

590

Middle Eastern (MID)

AF:

0.556

AC:

AN:

European-Non Finnish (NFE)

AF:

0.484

AC:

1379

AN:

2850

Other (OTH)

AF:

0.475

AC:

131

AN:

276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.520

AC:

79035

AN:

152124

Hom.:

21576

Cov.:

AF XY:

0.516

AC XY:

38361

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.362

AC:

15007

AN:

41492

American (AMR)

AF:

0.561

AC:

8586

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

2059

AN:

3472

East Asian (EAS)

AF:

0.493

AC:

2548

AN:

5166

South Asian (SAS)

AF:

0.336

AC:

1625

AN:

4830

European-Finnish (FIN)

AF:

0.572

AC:

6052

AN:

10588

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.608

AC:

41312

AN:

67962

Other (OTH)

AF:

0.544

AC:

1149

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1893

3787

5680

7574

9467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.559

Hom.:

2949

Bravo

AF:

0.517

Asia WGS

AF:

0.404

AC:

1407

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over