rs13306114

Variant names:

• chr22-24433302-C-A
• rs13306114
• ENST00000358654.2:n.*1033C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-24433302-C-A
• chr22-24433302-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000358654.2(SPECC1L-ADORA2A):​n.*1033C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000956 in 1,046,472 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: 9.6e-7 (0 hom.)
• Consequence: SPECC1L-ADORA2A ENST00000358654.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA2A	NM_000675.6	c.-103C>A		5_prime_UTR_variant	Exon 2 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.*1033C>A		non_coding_transcript_exon_variant	Exon 19 of 20	2		ENSP00000351480.2
ADORA2A	ENST00000337539.12	c.-103C>A		5_prime_UTR_variant	Exon 2 of 3	1	NM_000675.6	ENSP00000336630.6
SPECC1L-ADORA2A	ENST00000358654.2	n.*1033C>A		3_prime_UTR_variant	Exon 19 of 20	2		ENSP00000351480.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.56e-7 AC: 1 AN: 1046472 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 521162

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24488

American (AMR) AF: 0.00 AC: 0 AN: 29842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19428

East Asian (EAS) AF: 0.00 AC: 0 AN: 33992

South Asian (SAS) AF: 0.00 AC: 0 AN: 64002

European-Finnish (FIN) AF: 0.0000304 AC: 1 AN: 32896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 792678

Other (OTH) AF: 0.00 AC: 0 AN: 45860

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.87
PhyloP100		-0.77
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs13306114; hg19: chr22-24829270;