rs2051582

Variant names:

• chr22-37162316-G-A
• rs2051582
• NM_001346222.1:c.-34+12678C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346222.1(IL2RB):​c.-34+12678C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,026 control chromosomes in the GnomAD database, including 2,513 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 0.18 (2513 hom., cov: 31)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 11 publications found

Genes affected

IL2RB (HGNC:6009): (interleukin 2 receptor subunit beta) The interleukin 2 receptor, which is involved in T cell-mediated immune responses, is present in 3 forms with respect to ability to bind interleukin 2. The low affinity form is a monomer of the alpha subunit and is not involved in signal transduction. The intermediate affinity form consists of an alpha/beta subunit heterodimer, while the high affinity form consists of an alpha/beta/gamma subunit heterotrimer. Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. The protein encoded by this gene represents the beta subunit and is a type I membrane protein. The use of alternative promoters results in multiple transcript variants encoding the same protein. The protein is primarily expressed in the hematopoietic system. The use by some variants of an alternate promoter in an upstream long terminal repeat (LTR) results in placenta-specific expression. [provided by RefSeq, Sep 2016]

IL2RB Gene-Disease associations (from GenCC):

• immunodeficiency 63 with lymphoproliferation and autoimmunity

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_001346222.1	c.-34+12678C>T		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-34+12642C>T		intron_variant	Intron 1 of 9		NP_001333152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000429622.6	c.-34+12642C>T		intron_variant	Intron 1 of 9	4		ENSP00000402685.2
IL2RB	ENST00000445595.2	c.-224-333C>T		intron_variant	Intron 1 of 10	4		ENSP00000401020.2
IL2RB	ENST00000453962.6	c.-34+12678C>T		intron_variant	Intron 1 of 9	4		ENSP00000403731.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26991 AN: 151908 Hom.: 2515 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.178 AC: 27009 AN: 152026 Hom.: 2513 Cov.: 31 AF XY: 0.176 AC XY: 13103 AN XY: 74322

African (AFR) AF: 0.117 AC: 4851 AN: 41438

American (AMR) AF: 0.138 AC: 2106 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3468

East Asian (EAS) AF: 0.170 AC: 877 AN: 5162

South Asian (SAS) AF: 0.153 AC: 740 AN: 4824

European-Finnish (FIN) AF: 0.241 AC: 2542 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14510 AN: 67978

Other (OTH) AF: 0.182 AC: 385 AN: 2112

Alfa AF: 0.201 Hom.: 10478

Bravo AF: 0.171

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.27
PhyloP100		-3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2051582; hg19: chr22-37558356;