6-137147787-C-T

Variant names:

• chr6-137147787-C-T
• rs1411166898
• NM_052962.3:c.577G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.115

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]

ACMG classification

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
IL22RA2	NM_052962.3	c.577G>A	p.Val193Ile	missense_variant	Exon 6 of 7	ENST00000296980.7	NP_443194.1
IL22RA2	NM_181309.2	c.481G>A	p.Val161Ile	missense_variant	Exon 5 of 6		NP_851826.1
IL22RA2	NM_181310.2	c.377-2014G>A		intron_variant	Intron 4 of 4		NP_851827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL22RA2	ENST00000296980.7	c.577G>A	p.Val193Ile	missense_variant	Exon 6 of 7	1	NM_052962.3	ENSP00000296980.2
IL22RA2	ENST00000349184.9	c.481G>A	p.Val161Ile	missense_variant	Exon 5 of 6	1		ENSP00000296979.4
IL22RA2	ENST00000339602.3	c.377-2014G>A		intron_variant	Intron 4 of 4	1		ENSP00000340920.3

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

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

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

Other links and lift over

dbSNP: rs1411166898; hg19: chr6-137468924;