rs12722516

Positions:

• chr10-6039254-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000379959.8(IL2RA):​c.65-13229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 152,370 control chromosomes in the GnomAD database, including 50 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 0.021 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL2RA ENST00000379959.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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=-0.94).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.021 (3198/152370) while in subpopulation NFE AF= 0.0311 (2114/68030). AF 95% confidence interval is 0.03. There are 50 homozygotes in gnomad4. There are 1533 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL2RA	NM_000417.3	c.65-13229T>C		intron_variant		ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2	c.65-13229T>C		intron_variant			NP_001295171.1
IL2RA	NM_001308243.2	c.65-13229T>C		intron_variant			NP_001295172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8	c.65-13229T>C		intron_variant		1	NM_000417.3	ENSP00000369293	P1

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3201 AN: 152252 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00581

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0205

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0210 AC: 3198 AN: 152370 Hom.: 50 Cov.: 33 AF XY: 0.0206 AC XY: 1533 AN XY: 74510

Gnomad4 AFR AF: 0.00579

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0250 Hom.: 7

Bravo AF: 0.0185

Asia WGS AF: 0.00607 AC: 21 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.52

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: rs12722516; hg19: chr10-6081217;