6-137154721-T-C

Variant names:

• chr6-137154721-T-C
• rs7774349
• NM_052962.3:c.472+220A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052962.3(IL22RA2):​c.472+220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,014 control chromosomes in the GnomAD database, including 29,221 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 0.60 (29221 hom., cov: 31)
• Consequence: IL22RA2 NM_052962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL22RA2	NM_052962.3	c.472+220A>G		intron_variant	Intron 5 of 6	ENST00000296980.7	NP_443194.1
IL22RA2	NM_181309.2	c.376+220A>G		intron_variant	Intron 4 of 5		NP_851826.1
IL22RA2	NM_181310.2	c.376+220A>G		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.472+220A>G		intron_variant	Intron 5 of 6	1	NM_052962.3	ENSP00000296980.2
IL22RA2	ENST00000349184.9	c.376+220A>G		intron_variant	Intron 4 of 5	1		ENSP00000296979.4
IL22RA2	ENST00000339602.3	c.376+220A>G		intron_variant	Intron 4 of 4	1		ENSP00000340920.3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90430 AN: 151896 Hom.: 29160 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.634

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.596 AC: 90542 AN: 152014 Hom.: 29221 Cov.: 31 AF XY: 0.593 AC XY: 44087 AN XY: 74286

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.638

Alfa AF: 0.505 Hom.: 33764

Bravo AF: 0.613

Asia WGS AF: 0.735 AC: 2554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.038
DANN	Benign	0.39

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: rs7774349; hg19: chr6-137475858;