Variant 6-137154961-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_052962.3(IL22RA2):c.452G>A(p.Arg151Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

IL22RA2
NM_052962.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Variant links:

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]

IL22RA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a site Critical for IL22-binding (size 0) in uniprot entity I22R2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL22RA2	NM_052962.3 linkuse as main transcript	c.452G>A	p.Arg151Gln	missense_variant	5/7	ENST00000296980.7
IL22RA2	NM_181309.2 linkuse as main transcript	c.356G>A	p.Arg119Gln	missense_variant	4/6
IL22RA2	NM_181310.2 linkuse as main transcript	c.356G>A	p.Arg119Gln	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL22RA2	ENST00000296980.7 linkuse as main transcript	c.452G>A	p.Arg151Gln	missense_variant	5/7	1	NM_052962.3		Q969J5-1
IL22RA2	ENST00000349184.9 linkuse as main transcript	c.356G>A	p.Arg119Gln	missense_variant	4/6	1		P1	Q969J5-2
IL22RA2	ENST00000339602.3 linkuse as main transcript	c.356G>A	p.Arg119Gln	missense_variant	4/5	1			Q969J5-3

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251094

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000250

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.000249

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2022

The c.452G>A (p.R151Q) alteration is located in exon 5 (coding exon 4) of the IL22RA2 gene. This alteration results from a G to A substitution at nucleotide position 452, causing the arginine (R) at amino acid position 151 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

.;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Uncertain

-0.074

MutationAssessor

Pathogenic

3.5

.;H;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.67

MVP

0.51

MPC

0.076

ClinPred

0.72

GERP RS

5.8

Varity_R

0.95

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over