rs2069762

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000586.4(IL2):​c.-385T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 166,840 control chromosomes in the GnomAD database, including 6,559 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 0.25 ( 5685 hom., cov: 32)
Exomes 𝑓: 0.33 ( 874 hom. )

Consequence

IL2
NM_000586.4 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL2NM_000586.4 linkc.-385T>G upstream_gene_variant ENST00000226730.5 NP_000577.2 P60568Q0GK43

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL2ENST00000226730.5 linkc.-385T>G upstream_gene_variant 1 NM_000586.4 ENSP00000226730.5 P60568

Frequencies

GnomAD3 genomes
AF:
0.248
AC:
37699
AN:
151794
Hom.:
5671
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0736
Gnomad AMI
AF:
0.346
Gnomad AMR
AF:
0.298
Gnomad ASJ
AF:
0.430
Gnomad EAS
AF:
0.339
Gnomad SAS
AF:
0.504
Gnomad FIN
AF:
0.292
Gnomad MID
AF:
0.506
Gnomad NFE
AF:
0.299
Gnomad OTH
AF:
0.297
GnomAD4 exome
AF:
0.328
AC:
4903
AN:
14926
Hom.:
874
AF XY:
0.331
AC XY:
2429
AN XY:
7336
show subpopulations
Gnomad4 AFR exome
AF:
0.0876
Gnomad4 AMR exome
AF:
0.318
Gnomad4 ASJ exome
AF:
0.452
Gnomad4 EAS exome
AF:
0.375
Gnomad4 SAS exome
AF:
0.515
Gnomad4 FIN exome
AF:
0.343
Gnomad4 NFE exome
AF:
0.317
Gnomad4 OTH exome
AF:
0.330
GnomAD4 genome
AF:
0.248
AC:
37733
AN:
151914
Hom.:
5685
Cov.:
32
AF XY:
0.254
AC XY:
18877
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0737
Gnomad4 AMR
AF:
0.299
Gnomad4 ASJ
AF:
0.430
Gnomad4 EAS
AF:
0.339
Gnomad4 SAS
AF:
0.506
Gnomad4 FIN
AF:
0.292
Gnomad4 NFE
AF:
0.299
Gnomad4 OTH
AF:
0.302
Alfa
AF:
0.286
Hom.:
3236
Bravo
AF:
0.237
Asia WGS
AF:
0.422
AC:
1467
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
19
DANN
Benign
0.67

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2069762; hg19: chr4-123377980; API