Genetic Variant IL22RA2:p.Val226Ile (chr6-137145740-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052962.3(IL22RA2):c.676G>A(p.Val226Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V226F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

IL22RA2
NM_052962.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00200

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038935423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL22RA2	NM_052962.3 link	c.676G>A	p.Val226Ile	missense_variant	Exon 7 of 7	ENST00000296980.7	NP_443194.1	Q969J5-1
IL22RA2	NM_181309.2 link	c.580G>A	p.Val194Ile	missense_variant	Exon 6 of 6		NP_851826.1	Q969J5-2
IL22RA2	NM_181310.2 link	c.*17G>A		3_prime_UTR_variant	Exon 5 of 5		NP_851827.1	Q969J5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL22RA2	ENST00000296980.7 link	c.676G>A	p.Val226Ile	missense_variant	Exon 7 of 7	1	NM_052962.3	ENSP00000296980.2	Q969J5-1
IL22RA2	ENST00000349184.9 link	c.580G>A	p.Val194Ile	missense_variant	Exon 6 of 6	1		ENSP00000296979.4	Q969J5-2
IL22RA2	ENST00000339602 link	c.*17G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000340920.3	Q969J5-3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000279

AC:

AN:

250962

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000524

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

Bravo

AF:

0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.8

DANN

Benign

0.77

DEOGEN2

Benign

0.0083

.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

.;L

PrimateAI

Benign

0.27

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.070

Sift

Benign

0.44

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.0050

B;B

Vest4

0.044

MutPred

0.47

.;Loss of loop (P = 0.1242);

MVP

0.048

MPC

0.013

ClinPred

0.018

GERP RS

0.84

Varity_R

0.12

gMVP

0.19

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over