Genetic Variant IL22RA2:p.Val226Leu (chr6-137145740-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052962.3(IL22RA2):c.676G>C(p.Val226Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06050825).

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>C	p.Val226Leu	missense	Exon 7 of 7	NP_443194.1	Q969J5-1
IL22RA2	NM_181309.2		c.580G>C	p.Val194Leu	missense	Exon 6 of 6	NP_851826.1	Q969J5-2
IL22RA2	NM_181310.2		c.*17G>C		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>C	p.Val226Leu	missense	Exon 7 of 7	ENSP00000296980.2	Q969J5-1
IL22RA2	ENST00000349184.9	TSL:1	c.580G>C	p.Val194Leu	missense	Exon 6 of 6	ENSP00000296979.4	Q969J5-2
IL22RA2	ENST00000339602.3	TSL:1	c.*17G>C		3_prime_UTR	Exon 5 of 5	ENSP00000340920.3	Q969J5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250962

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44690

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:

8.99e-7

AC:

AN:

1111908

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.75

M_CAP

Benign

0.0070

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.0020

PrimateAI

Benign

0.31

PROVEAN

Benign

0.090

REVEL

Benign

0.074

Sift

Benign

0.58

Sift4G

Benign

0.085

Polyphen

0.063

Vest4

0.20

MutPred

0.50

Gain of loop (P = 0.1069)

MVP

0.081

MPC

0.015

ClinPred

0.037

GERP RS

0.84

Varity_R

0.16

gMVP

0.39

Mutation Taster

=91/9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over