rs2069777

Variant names:

• chr4-122455282-G-A
• rs2069777
• NM_000586.4:c.207+862C>T

Variant summary

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

The NM_000586.4(IL2):​c.207+862C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 151,888 control chromosomes in the GnomAD database, including 256 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 0.049 (256 hom., cov: 32)
• Consequence: IL2 NM_000586.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

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.207+862C>T		intron	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.207+862C>T		intron	N/A	ENSP00000226730.5
	IL2	ENST00000477645.1	TSL:3	n.297+862C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 7460 AN: 151770 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0491 AC: 7452 AN: 151888 Hom.: 256 Cov.: 32 AF XY: 0.0497 AC XY: 3693 AN XY: 74266

African (AFR) AF: 0.0104 AC: 431 AN: 41494

American (AMR) AF: 0.0378 AC: 576 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5166

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4820

European-Finnish (FIN) AF: 0.0941 AC: 996 AN: 10590

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5012 AN: 67814

Other (OTH) AF: 0.0441 AC: 93 AN: 2110

Alfa AF: 0.0634 Hom.: 59

Bravo AF: 0.0428

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2069777; hg19: chr4-123376437;