6-137147787-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.115
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 3860252.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL22RA2NM_052962.3 linkc.577G>A p.Val193Ile missense_variant Exon 6 of 7 ENST00000296980.7 NP_443194.1 Q969J5-1
IL22RA2NM_181309.2 linkc.481G>A p.Val161Ile missense_variant Exon 5 of 6 NP_851826.1 Q969J5-2
IL22RA2NM_181310.2 linkc.377-2014G>A intron_variant Intron 4 of 4 NP_851827.1 Q969J5-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL22RA2ENST00000296980.7 linkc.577G>A p.Val193Ile missense_variant Exon 6 of 7 1 NM_052962.3 ENSP00000296980.2 Q969J5-1
IL22RA2ENST00000349184.9 linkc.481G>A p.Val161Ile missense_variant Exon 5 of 6 1 ENSP00000296979.4 Q969J5-2
IL22RA2ENST00000339602.3 linkc.377-2014G>A intron_variant Intron 4 of 4 1 ENSP00000340920.3 Q969J5-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456964
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725144
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000271
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 30, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.0050
DANN
Benign
0.18
DEOGEN2
Benign
0.0065
.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0041
N
LIST_S2
Benign
0.32
T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.035
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.67
.;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.18
N;N
REVEL
Benign
0.036
Sift
Benign
0.94
T;T
Sift4G
Benign
0.74
T;T
Polyphen
0.0080
B;B
Vest4
0.039
MutPred
0.51
.;Loss of ubiquitination at K189 (P = 0.0768);
MVP
0.048
MPC
0.011
ClinPred
0.029
T
GERP RS
-2.1
Varity_R
0.098
gMVP
0.14

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.

Other links and lift over

dbSNP: rs1411166898; hg19: chr6-137468924; API