rs2069763

Variant names:

• chr4-122456327-C-A
• rs2069763
• NM_000586.4:c.114G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-122456327-C-A
• chr4-122456327-C-G
• chr4-122456327-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000586.4(IL2):​c.114G>T​(p.Leu38Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,606,330 control chromosomes in the GnomAD database, including 93,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (7518 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86113 hom.)
• Consequence: IL2 NM_000586.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 4-122456327-C-A is Benign according to our data. Variant chr4-122456327-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2	NM_000586.4	c.114G>T	p.Leu38Leu	synonymous_variant	Exon 1 of 4	ENST00000226730.5	NP_000577.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2	ENST00000226730.5	c.114G>T	p.Leu38Leu	synonymous_variant	Exon 1 of 4	1	NM_000586.4	ENSP00000226730.5
IL2	ENST00000477645.1	n.114G>T		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43941 AN: 151608 Hom.: 7517 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.271

GnomAD2 exomes AF: 0.356 AC: 88751 AN: 249066 AF XY: 0.347

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.473

Gnomad FIN exome AF: 0.475

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.335 AC: 487565 AN: 1454604 Hom.: 86113 Cov.: 32 AF XY: 0.332 AC XY: 240311 AN XY: 723892

Gnomad4 AFR exome AF: 0.0987 AC: 3296 AN: 33390

Gnomad4 AMR exome AF: 0.487 AC: 21627 AN: 44448

Gnomad4 ASJ exome AF: 0.220 AC: 5729 AN: 26014

Gnomad4 EAS exome AF: 0.492 AC: 19476 AN: 39594

Gnomad4 SAS exome AF: 0.270 AC: 23245 AN: 86056

Gnomad4 FIN exome AF: 0.470 AC: 25059 AN: 53302

Gnomad4 NFE exome AF: 0.335 AC: 370198 AN: 1105938

Gnomad4 Remaining exome AF: 0.299 AC: 17984 AN: 60116

GnomAD4 genome AF: 0.290 AC: 43943 AN: 151726 Hom.: 7518 Cov.: 32 AF XY: 0.297 AC XY: 21980 AN XY: 74130

Gnomad4 AFR AF: 0.116 AC: 0.115734 AN: 0.115734

Gnomad4 AMR AF: 0.395 AC: 0.395156 AN: 0.395156

Gnomad4 ASJ AF: 0.210 AC: 0.210283 AN: 0.210283

Gnomad4 EAS AF: 0.477 AC: 0.476726 AN: 0.476726

Gnomad4 SAS AF: 0.262 AC: 0.262013 AN: 0.262013

Gnomad4 FIN AF: 0.472 AC: 0.471906 AN: 0.471906

Gnomad4 NFE AF: 0.338 AC: 0.338009 AN: 0.338009

Gnomad4 OTH AF: 0.271 AC: 0.271388 AN: 0.271388

Alfa AF: 0.318 Hom.: 22765

Bravo AF: 0.279

Asia WGS AF: 0.300 AC: 1042 AN: 3478

EpiCase AF: 0.309

EpiControl AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.5
DANN	Benign	0.59
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

Publications

LitVar

Other links and lift over

dbSNP: rs2069763; hg19: chr4-123377482; COSMIC: COSV56985306;