22-24441941-CT-CTT

Variant names:

• chr22-24441941-C-CT
• rs35060421
• ENST00000358654.2:n.*2832dupT

Variant summary

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

The ENST00000358654.2(SPECC1L-ADORA2A):​n.*2832dupT variant causes a non coding transcript exon 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: SPECC1L-ADORA2A ENST00000358654.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 6 publications found

Genes affected

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 (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)

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA2A	NM_000675.6	c.*458dupT		3_prime_UTR_variant	Exon 3 of 3	ENST00000337539.12	NP_000666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPECC1L-ADORA2A	ENST00000358654.2	n.*2832dupT		non_coding_transcript_exon_variant	Exon 20 of 20	2		ENSP00000351480.2
ADORA2A	ENST00000337539.12	c.*458dupT		3_prime_UTR_variant	Exon 3 of 3	1	NM_000675.6	ENSP00000336630.6
SPECC1L-ADORA2A	ENST00000358654.2	n.*2832dupT		3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000351480.2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78968 AN: 152006 Hom.: 21559 Cov.: 0

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.: 0 AF XY: 0.483 AC XY: 1149 AN XY: 2378

African (AFR) AF: 0.284 AC: 62 AN: 218

American (AMR) AF: 0.448 AC: 43 AN: 96

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 90 AN: 180

East Asian (EAS) AF: 0.468 AC: 116 AN: 248

South Asian (SAS) AF: 0.258 AC: 16 AN: 62

European-Finnish (FIN) AF: 0.522 AC: 308 AN: 590

Middle Eastern (MID) AF: 0.556 AC: 10 AN: 18

European-Non Finnish (NFE) AF: 0.484 AC: 1379 AN: 2850

Other (OTH) AF: 0.475 AC: 131 AN: 276

GnomAD4 genome AF: 0.520 AC: 79035 AN: 152124 Hom.: 21576 Cov.: 0 AF XY: 0.516 AC XY: 38361 AN XY: 74372

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66
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: rs35060421; hg19: chr22-24837909; COSMIC: COSV58378690; COSMIC: COSV58378690;