6-137144950-C-T

Position:

• chr6-137144950-C-T

Variant summary

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

The NM_052962.3(IL22RA2):​c.*674G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,158 control chromosomes in the GnomAD database, including 57,066 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 0.86 (57066 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL22RA2 NM_052962.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL22RA2	NM_052962.3	c.*674G>A		3_prime_UTR_variant	7/7	ENST00000296980.7	NP_443194.1
IL22RA2	NM_181309.2	c.*674G>A		3_prime_UTR_variant	6/6		NP_851826.1
IL22RA2	NM_181310.2	c.*807G>A		3_prime_UTR_variant	5/5		NP_851827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL22RA2	ENST00000296980.7	c.*674G>A		3_prime_UTR_variant	7/7	1	NM_052962.3	ENSP00000296980.2
IL22RA2	ENST00000349184.9	c.*674G>A		3_prime_UTR_variant	6/6	1		ENSP00000296979.4
IL22RA2	ENST00000339602.3	c.*807G>A		3_prime_UTR_variant	5/5	1		ENSP00000340920.3

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131208 AN: 152040 Hom.: 56994 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.848

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.863 AC: 131340 AN: 152158 Hom.: 57066 Cov.: 32 AF XY: 0.866 AC XY: 64441 AN XY: 74388

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.850

Alfa AF: 0.809 Hom.: 44751

Bravo AF: 0.865

Asia WGS AF: 0.959 AC: 3318 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.47
DANN	Benign	0.35

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: rs28366; hg19: chr6-137466087; COSMIC: COSV51662831;