rs7899538

Positions:

• chr10-6017935-C-A
• chr10-6017935-C-G
• chr10-6017935-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000417.3(IL2RA):​c.794+118G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 791,480 control chromosomes in the GnomAD database, including 7,632 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 0.11 (1221 hom., cov: 31)
  • Exomes 𝑓: 0.13 (6411 hom.)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

Genes affected

IL2RA (HGNC:6008): (interleukin 2 receptor subunit alpha) The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL2 receptor. Homodimeric alpha chains (IL2RA) result in low-affinity receptor, while homodimeric beta (IL2RB) chains produce a medium-affinity receptor. Normally an integral-membrane protein, soluble IL2RA has been isolated and determined to result from extracellular proteolyisis. Alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is presently unknown. Mutations in this gene are associated with interleukin 2 receptor alpha deficiency. Patients with severe Coronavirus Disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have significantly elevated levels of IL2R in their plasma. Similarly, serum IL-2R levels are found to be elevated in patients with different types of carcinomas. Certain IL2RA and IL2RB gene polymorphisms have been associated with lung cancer risk. [provided by RefSeq, Jul 2020]

IL2RA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL2RA	NM_000417.3	c.794+118G>T		intron_variant		ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2	c.578+118G>T		intron_variant			NP_001295171.1
IL2RA	NM_001308243.2	c.506+118G>T		intron_variant			NP_001295172.1
LOC124902368	XR_007062042.1	n.143+1603C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8	c.794+118G>T		intron_variant		1	NM_000417.3	ENSP00000369293.3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17124 AN: 151844 Hom.: 1219 Cov.: 31

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.133 AC: 85285 AN: 639518 Hom.: 6411 AF XY: 0.133 AC XY: 45185 AN XY: 340188

Gnomad4 AFR exome AF: 0.0605

Gnomad4 AMR exome AF: 0.0713

Gnomad4 ASJ exome AF: 0.0918

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.113 AC: 17136 AN: 151962 Hom.: 1221 Cov.: 31 AF XY: 0.116 AC XY: 8623 AN XY: 74246

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.0769

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.104

Alfa AF: 0.117 Hom.: 1548

Bravo AF: 0.0985

Asia WGS AF: 0.205 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.70

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: rs7899538; hg19: chr10-6059898;