Variant 6-137154943-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_052962.3(IL22RA2):c.470A>C(p.Glu157Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000123 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

IL22RA2
NM_052962.3 missense, splice_region

Scores

Splicing: ADA: 0.05548

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL22RA2	NM_052962.3 linkuse as main transcript	c.470A>C	p.Glu157Ala	missense_variant, splice_region_variant	5/7	ENST00000296980.7
IL22RA2	NM_181309.2 linkuse as main transcript	c.374A>C	p.Glu125Ala	missense_variant, splice_region_variant	4/6
IL22RA2	NM_181310.2 linkuse as main transcript	c.374A>C	p.Glu125Ala	missense_variant, splice_region_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL22RA2	ENST00000296980.7 linkuse as main transcript	c.470A>C	p.Glu157Ala	missense_variant, splice_region_variant	5/7	1	NM_052962.3		Q969J5-1
IL22RA2	ENST00000349184.9 linkuse as main transcript	c.374A>C	p.Glu125Ala	missense_variant, splice_region_variant	4/6	1		P1	Q969J5-2
IL22RA2	ENST00000339602.3 linkuse as main transcript	c.374A>C	p.Glu125Ala	missense_variant, splice_region_variant	4/5	1			Q969J5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727144

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:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.470A>C (p.E157A) alteration is located in exon 5 (coding exon 4) of the IL22RA2 gene. This alteration results from a A to C substitution at nucleotide position 470, causing the glutamic acid (E) at amino acid position 157 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;T;T

M_CAP

Uncertain

0.091

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Uncertain

-0.057

MutationAssessor

Pathogenic

3.3

.;M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.96

D;D;D

Vest4

0.73

MutPred

0.76

.;Gain of MoRF binding (P = 0.0699);.;

MVP

0.53

MPC

0.044

ClinPred

0.99

GERP RS

4.6

Varity_R

0.79

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.055

dbscSNV1_RF

Benign

0.33

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over