Genetic Variant IL22RA2:p.Val193Ile (chr6-137147787-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_052962.3(IL22RA2):c.577G>A(p.Val193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,964 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IL22RA2
NM_052962.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.115

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0347732).

BP6

Variant 6-137147787-C-T is Benign according to our data. Variant chr6-137147787-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3860252.Status of the report is criteria_provided_single_submitter, 1 stars.

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.577G>A	p.Val193Ile	missense	Exon 6 of 7	NP_443194.1	Q969J5-1
IL22RA2	NM_181309.2		c.481G>A	p.Val161Ile	missense	Exon 5 of 6	NP_851826.1	Q969J5-2
IL22RA2	NM_181310.2		c.377-2014G>A		intron	N/A	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.577G>A	p.Val193Ile	missense	Exon 6 of 7	ENSP00000296980.2	Q969J5-1
IL22RA2	ENST00000349184.9	TSL:1	c.481G>A	p.Val161Ile	missense	Exon 5 of 6	ENSP00000296979.4	Q969J5-2
IL22RA2	ENST00000339602.3	TSL:1	c.377-2014G>A		intron	N/A	ENSP00000340920.3	Q969J5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

250570

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456964

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33348

American (AMR)

AF:

0.00

AC:

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1107868

Other (OTH)

AF:

0.00

AC:

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0050

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.32

M_CAP

Benign

0.0048

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

PhyloP100

-0.12

PrimateAI

Benign

0.29

PROVEAN

Benign

0.18

REVEL

Benign

0.036

Sift

Benign

0.94

Sift4G

Benign

0.74

Polyphen

0.0080

Vest4

0.039

MutPred

0.51

Loss of ubiquitination at K189 (P = 0.0768)

MVP

0.048

MPC

0.011

ClinPred

0.029

GERP RS

-2.1

Varity_R

0.098

gMVP

0.14

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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