Genetic Variant IL22RA2:p.Val226Ile (chr6-137145740-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 16/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052962.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL22RA2	NM_052962.3	MANE Select	c.676G>A	p.Val226Ile	missense	Exon 7 of 7	NP_443194.1	Q969J5-1
IL22RA2	NM_181309.2		c.580G>A	p.Val194Ile	missense	Exon 6 of 6	NP_851826.1	Q969J5-2
IL22RA2	NM_181310.2		c.*17G>A		3_prime_UTR	Exon 5 of 5	NP_851827.1	Q969J5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL22RA2	ENST00000296980.7	TSL:1 MANE Select	c.676G>A	p.Val226Ile	missense	Exon 7 of 7	ENSP00000296980.2	Q969J5-1
IL22RA2	ENST00000349184.9	TSL:1	c.580G>A	p.Val194Ile	missense	Exon 6 of 6	ENSP00000296979.4	Q969J5-2
IL22RA2	ENST00000339602.3	TSL:1	c.*17G>A		3_prime_UTR	Exon 5 of 5	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

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

250962

AF XY:

0.0000221

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 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

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000157

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111908

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.000524

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.8

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.64

M_CAP

Benign

0.0033

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

PhyloP100

0.0020

PrimateAI

Benign

0.27

PROVEAN

Benign

0.060

REVEL

Benign

0.070

Sift

Benign

0.44

Sift4G

Benign

0.76

Polyphen

0.0050

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

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over