6-137156686-C-T

Variant names:

• chr6-137156686-C-T
• rs2064501
• NM_052962.3:c.293+73G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052962.3(IL22RA2):​c.293+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,557,572 control chromosomes in the GnomAD database, including 209,565 homozygotes. 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: 𝑓 0.59 (29140 hom., cov: 31)
  • Exomes 𝑓: 0.50 (180425 hom.)
• Consequence: IL22RA2 NM_052962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908

Genes affected

IL22RA2 (HGNC:14901): (interleukin 22 receptor subunit alpha 2) This gene encodes a member of the class II cytokine receptor family. The encoded soluble protein specifically binds to and inhibits interleukin 22 activity by blocking the interaction of interleukin 22 with its cell surface receptor. The encoded protein may be important in the regulation of inflammatory response, and has been implicated in the regulation of tumorigenesis in the colon. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL22RA2	NM_052962.3	c.293+73G>A		intron_variant	Intron 4 of 6	ENST00000296980.7	NP_443194.1
IL22RA2	NM_181309.2	c.198-1567G>A		intron_variant	Intron 3 of 5		NP_851826.1
IL22RA2	NM_181310.2	c.198-1567G>A		intron_variant	Intron 3 of 4		NP_851827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL22RA2	ENST00000296980.7	c.293+73G>A		intron_variant	Intron 4 of 6	1	NM_052962.3	ENSP00000296980.2
IL22RA2	ENST00000349184.9	c.198-1567G>A		intron_variant	Intron 3 of 5	1		ENSP00000296979.4
IL22RA2	ENST00000339602.3	c.198-1567G>A		intron_variant	Intron 3 of 4	1		ENSP00000340920.3

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90315 AN: 151938 Hom.: 29078 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.499 AC: 701940 AN: 1405516 Hom.: 180425 AF XY: 0.504 AC XY: 348715 AN XY: 692206

Gnomad4 AFR exome AF: 0.867

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.595 AC: 90429 AN: 152056 Hom.: 29140 Cov.: 31 AF XY: 0.593 AC XY: 44045 AN XY: 74332

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.638

Alfa AF: 0.518 Hom.: 12112

Bravo AF: 0.612

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.77
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2064501; hg19: chr6-137477823;