rs12722574

Variant names:

• chr10-6024499-G-A
• rs12722574
• NM_000417.3:c.257-145C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-6024499-G-A
• chr10-6024499-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000417.3(IL2RA):​c.257-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 678,636 control chromosomes in the GnomAD database, including 17,997 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 0.26 (6096 hom., cov: 33)
  • Exomes 𝑓: 0.20 (11901 hom.)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 13 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RA	NM_000417.3	MANE Select	c.257-145C>T		intron	N/A	NP_000408.1
	IL2RA	NM_001308242.2		c.257-145C>T		intron	N/A	NP_001295171.1
	IL2RA	NM_001308243.2		c.257-145C>T		intron	N/A	NP_001295172.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RA	ENST00000379959.8	TSL:1 MANE Select	c.257-145C>T		intron	N/A	ENSP00000369293.3
	IL2RA	ENST00000379954.5	TSL:1	c.257-145C>T		intron	N/A	ENSP00000369287.1
	IL2RA	ENST00000447847.2	TSL:1	c.257-145C>T		intron	N/A	ENSP00000402024.2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39429 AN: 152006 Hom.: 6087 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.203 AC: 107005 AN: 526512 Hom.: 11901 AF XY: 0.204 AC XY: 57150 AN XY: 279866

African (AFR) AF: 0.438 AC: 6379 AN: 14552

American (AMR) AF: 0.117 AC: 3396 AN: 29136

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 3628 AN: 16446

East Asian (EAS) AF: 0.158 AC: 5033 AN: 31760

South Asian (SAS) AF: 0.226 AC: 11914 AN: 52708

European-Finnish (FIN) AF: 0.151 AC: 6045 AN: 40064

Middle Eastern (MID) AF: 0.193 AC: 741 AN: 3840

European-Non Finnish (NFE) AF: 0.206 AC: 63622 AN: 308988

Other (OTH) AF: 0.215 AC: 6247 AN: 29018

GnomAD4 genome AF: 0.259 AC: 39468 AN: 152124 Hom.: 6096 Cov.: 33 AF XY: 0.253 AC XY: 18808 AN XY: 74376

African (AFR) AF: 0.435 AC: 18027 AN: 41486

American (AMR) AF: 0.169 AC: 2588 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.152 AC: 790 AN: 5184

South Asian (SAS) AF: 0.212 AC: 1023 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1383 AN: 10584

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14200 AN: 67976

Other (OTH) AF: 0.242 AC: 510 AN: 2110

Alfa AF: 0.237 Hom.: 1699

Bravo AF: 0.268

Asia WGS AF: 0.200 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.78
PhyloP100		-0.49
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: rs12722574; hg19: chr10-6066462; COSMIC: COSV56919561; COSMIC: COSV56919561;