rs7093069

Variant names:

• chr10-6021356-C-T
• rs7093069
• NM_000417.3:c.583+122G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency due to CD25 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• neonatal diabetes mellitus with congenital hypothyroidism

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• type 1 diabetes mellitus 10

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

LOC124902368 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL2RA	NM_000417.3	c.583+122G>A		intron_variant	Intron 4 of 7	ENST00000379959.8	NP_000408.1
LOC124902368	XR_007062042.1	n.164C>T		non_coding_transcript_exon_variant	Exon 3 of 3
IL2RA	NM_001308242.2	c.368-1415G>A		intron_variant	Intron 3 of 6		NP_001295171.1
IL2RA	NM_001308243.2	c.368-1857G>A		intron_variant	Intron 3 of 5		NP_001295172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8	c.583+122G>A		intron_variant	Intron 4 of 7	1	NM_000417.3	ENSP00000369293.3

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

African (AFR) AF: 0.236 AC: 4361 AN: 18452

American (AMR) AF: 0.0860 AC: 3305 AN: 38408

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 3853 AN: 20414

East Asian (EAS) AF: 0.156 AC: 5599 AN: 35996

South Asian (SAS) AF: 0.164 AC: 11282 AN: 68844

European-Finnish (FIN) AF: 0.143 AC: 6558 AN: 45732

Middle Eastern (MID) AF: 0.134 AC: 352 AN: 2620

European-Non Finnish (NFE) AF: 0.179 AC: 78486 AN: 437332

Other (OTH) AF: 0.177 AC: 6267 AN: 35388

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

African (AFR) AF: 0.229 AC: 9407 AN: 41080

American (AMR) AF: 0.121 AC: 1838 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3468

East Asian (EAS) AF: 0.148 AC: 755 AN: 5110

South Asian (SAS) AF: 0.153 AC: 728 AN: 4758

European-Finnish (FIN) AF: 0.122 AC: 1268 AN: 10376

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12386 AN: 67814

Other (OTH) AF: 0.175 AC: 368 AN: 2102

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
PhyloP100		-0.0020
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: rs7093069; hg19: chr10-6063319; COSMIC: COSV56919553; COSMIC: COSV56919553;