rs7093069

chr10-6021356-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.583+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 854,316 control chromosomes in the GnomAD database, including 13,486 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 0.18 (2629 hom., cov: 29)
  • Exomes 𝑓: 0.17 (10857 hom.)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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]

LOC124902368 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RA	NM_000417.3	c.583+122G>A		intron_variant		ENST00000379959.8
LOC124902368	XR_007062042.1	n.164C>T		non_coding_transcript_exon_variant	3/3
IL2RA	NM_001308242.2	c.368-1415G>A		intron_variant
IL2RA	NM_001308243.2	c.368-1857G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RA	ENST00000379959.8	c.583+122G>A		intron_variant		1	NM_000417.3	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27460 AN: 151012 Hom.: 2620 Cov.: 29

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.171 AC: 120063 AN: 703186 Hom.: 10857 AF XY: 0.171 AC XY: 64231 AN XY: 376500

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.0860

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.182 AC: 27495 AN: 151130 Hom.: 2629 Cov.: 29 AF XY: 0.177 AC XY: 13034 AN XY: 73754

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.175

Alfa AF: 0.186 Hom.: 388

Bravo AF: 0.183

Asia WGS AF: 0.171 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.1
Dann	Benign	0.29

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: rs7093069; hg19: chr10-6063319; COSMIC: COSV56919553; COSMIC: COSV56919553;