rs12722605

Variant names:

• chr10-6011200-T-A
• rs12722605
• NM_000417.3:c.*1672A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000417.3(IL2RA):​c.*1672A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,470 control chromosomes in the GnomAD database, including 1,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1202 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4 hom.)
• Consequence: IL2RA NM_000417.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02
• Publications: 22 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-6011200-T-A is Benign according to our data. Variant chr10-6011200-T-A is described in ClinVar as Benign. ClinVar VariationId is 300218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000417.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RA	NM_000417.3	MANE Select	c.*1672A>T		3_prime_UTR	Exon 8 of 8	NP_000408.1	P01589
	IL2RA	NM_001308242.2		c.*1672A>T		3_prime_UTR	Exon 7 of 7	NP_001295171.1	Q5W005
	IL2RA	NM_001308243.2		c.*1672A>T		3_prime_UTR	Exon 6 of 6	NP_001295172.1	H0Y5Z0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RA	ENST00000379959.8	TSL:1 MANE Select	c.*1672A>T		3_prime_UTR	Exon 8 of 8	ENSP00000369293.3	P01589
	IL2RA	ENST00000649218.1		n.2306A>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16317 AN: 152194 Hom.: 1202 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00730

Gnomad SAS AF: 0.0820

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.146 AC: 23 AN: 158 Hom.: 4 Cov.: 0 AF XY: 0.144 AC XY: 13 AN XY: 90

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.157 AC: 22 AN: 140

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.107 AC: 16312 AN: 152312 Hom.: 1202 Cov.: 32 AF XY: 0.103 AC XY: 7653 AN XY: 74484

African (AFR) AF: 0.0314 AC: 1307 AN: 41572

American (AMR) AF: 0.116 AC: 1767 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3470

East Asian (EAS) AF: 0.00732 AC: 38 AN: 5192

South Asian (SAS) AF: 0.0814 AC: 393 AN: 4828

European-Finnish (FIN) AF: 0.0757 AC: 803 AN: 10614

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10742 AN: 68024

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.146 Hom.: 1000

Bravo AF: 0.108

Asia WGS AF: 0.0470 AC: 162 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency due to CD25 deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.59
PhyloP100		-1.0
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: rs12722605; hg19: chr10-6053163;