rs184635827

Variant names:

• chr4-122456807-CAG-C
• rs56359050
• NM_000586.4:c.-369_-368delCT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000586.4(IL2):​c.-369_-368delCT variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 174,848 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: IL2 NM_000586.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• Publications: 1 publications found

Genes affected

IL2 (HGNC:6001): (interleukin 2) This gene is a member of the interleukin 2 (IL2) cytokine subfamily which includes IL4, IL7, IL9, IL15, IL21, erythropoietin, and thrombopoietin. The protein encoded by this gene is a secreted cytokine produced by activated CD4+ and CD8+ T lymphocytes, that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine (IL2R) is a heterotrimeric protein complex whose gamma chain is also shared by IL4 and IL7. The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli. [provided by RefSeq, Sep 2020]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 328 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000586.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2	NM_000586.4	MANE Select	c.-369_-368delCT		upstream_gene	N/A	NP_000577.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2	ENST00000226730.5	TSL:1 MANE Select	c.-369_-368delCT		upstream_gene	N/A	ENSP00000226730.5	P60568

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 329 AN: 151906 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00145

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.000307 AC: 7 AN: 22824 Hom.: 0 AF XY: 0.000446 AC XY: 5 AN XY: 11216

African (AFR) AF: 0.00231 AC: 2 AN: 864

American (AMR) AF: 0.00157 AC: 2 AN: 1276

Ashkenazi Jewish (ASJ) AF: 0.000888 AC: 1 AN: 1126

East Asian (EAS) AF: 0.00 AC: 0 AN: 2170

South Asian (SAS) AF: 0.00 AC: 0 AN: 548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14644

Other (OTH) AF: 0.00126 AC: 2 AN: 1588

GnomAD4 genome AF: 0.00216 AC: 328 AN: 152024 Hom.: 2 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74340

African (AFR) AF: 0.00718 AC: 298 AN: 41500

American (AMR) AF: 0.00144 AC: 22 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67904

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00214 Hom.: 0

Bravo AF: 0.00272

Asia WGS AF: 0.000578 AC: 3 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

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

Other links and lift over

dbSNP: rs56359050; hg19: chr4-123377962;