Genetic Variant IL22RA2:c.293+73G>A (chr6-137156686-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052962.3(IL22RA2):c.293+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,557,572 control chromosomes in the GnomAD database, including 209,565 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 29140 hom., cov: 31)

Exomes 𝑓: 0.50 ( 180425 hom. )

Consequence

IL22RA2
NM_052962.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.908

Publications

13 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

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	Effect	Exon Rank	Protein
IL22RA2	NM_052962.3	MANE Select	c.293+73G>A	intron	N/A	NP_443194.1
IL22RA2	NM_181309.2		c.198-1567G>A	intron	N/A	NP_851826.1
IL22RA2	NM_181310.2		c.198-1567G>A	intron	N/A	NP_851827.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL22RA2	ENST00000296980.7	TSL:1 MANE Select	c.293+73G>A	intron	N/A	ENSP00000296980.2
IL22RA2	ENST00000349184.9	TSL:1	c.198-1567G>A	intron	N/A	ENSP00000296979.4
IL22RA2	ENST00000339602.3	TSL:1	c.198-1567G>A	intron	N/A	ENSP00000340920.3

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90315

AN:

151938

Hom.:

29078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.472

Gnomad OTH

AF:

0.633

GnomAD4 exome

AF:

0.499

AC:

701940

AN:

1405516

Hom.:

180425

AF XY:

0.504

AC XY:

348715

AN XY:

692206

show subpopulations

African (AFR)

AF:

0.867

AC:

28011

AN:

32310

American (AMR)

AF:

0.491

AC:

20891

AN:

42516

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

15075

AN:

24826

East Asian (EAS)

AF:

0.703

AC:

27115

AN:

38594

South Asian (SAS)

AF:

0.631

AC:

52482

AN:

83222

European-Finnish (FIN)

AF:

0.428

AC:

22158

AN:

51760

Middle Eastern (MID)

AF:

0.587

AC:

3202

AN:

5456

European-Non Finnish (NFE)

AF:

0.469

AC:

501717

AN:

1069178

Other (OTH)

AF:

0.543

AC:

31289

AN:

57654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

16645

33289

49934

66578

83223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15676

31352

47028

62704

78380

<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

AF:

0.595

AC:

90429

AN:

152056

Hom.:

29140

Cov.:

AF XY:

0.593

AC XY:

44045

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.854

AC:

35458

AN:

41504

American (AMR)

AF:

0.505

AC:

7726

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

2117

AN:

3466

East Asian (EAS)

AF:

0.714

AC:

3698

AN:

5176

South Asian (SAS)

AF:

0.641

AC:

3096

AN:

4828

European-Finnish (FIN)

AF:

0.419

AC:

4415

AN:

10538

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.472

AC:

32102

AN:

67946

Other (OTH)

AF:

0.638

AC:

1348

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1646

3293

4939

6586

8232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.519

Hom.:

16372

Bravo

AF:

0.612

Asia WGS

AF:

0.732

AC:

2544

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.77

(source)

DANN

Benign

0.74

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over