rs12722596

Positions:

• chr10-6014331-T-C

Variant summary

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

The NM_000417.3(IL2RA):​c.795-1435A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,228 control chromosomes in the GnomAD database, including 596 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 0.076 (596 hom., cov: 31)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL2RA	NM_000417.3	c.795-1435A>G		intron_variant		ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2	c.579-1435A>G		intron_variant			NP_001295171.1
IL2RA	NM_001308243.2	c.507-1435A>G		intron_variant			NP_001295172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8	c.795-1435A>G		intron_variant		1	NM_000417.3	ENSP00000369293	P1

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11541 AN: 152110 Hom.: 596 Cov.: 31

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.0651

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.0770

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0759 AC: 11550 AN: 152228 Hom.: 596 Cov.: 31 AF XY: 0.0799 AC XY: 5944 AN XY: 74434

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.0984

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0835 Hom.: 81

Bravo AF: 0.0620

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.86

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: rs12722596; hg19: chr10-6056294;