rs6602391

Positions:

• chr10-6036069-G-A
• chr10-6036069-G-T

Variant summary

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

The NM_000417.3(IL2RA):​c.65-10044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,324 control chromosomes in the GnomAD database, including 948 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 0.091 (947 hom., cov: 32)
  • Exomes 𝑓: 0.083 (1 hom.)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RA	NM_000417.3	c.65-10044C>T		intron_variant		ENST00000379959.8
LOC107984201	XR_001747349.2	n.653+7G>A		splice_region_variant, intron_variant, non_coding_transcript_variant
IL2RA	NM_001308242.2	c.65-10044C>T		intron_variant
IL2RA	NM_001308243.2	c.65-10044C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RA	ENST00000379959.8	c.65-10044C>T		intron_variant		1	NM_000417.3	P1
	ENST00000440436.1	n.221G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13887 AN: 152158 Hom.: 946 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0833 AC: 4 AN: 48 Hom.: 1 Cov.: 0 AF XY: 0.0476 AC XY: 2 AN XY: 42

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0714

GnomAD4 genome AF: 0.0913 AC: 13901 AN: 152276 Hom.: 947 Cov.: 32 AF XY: 0.0891 AC XY: 6633 AN XY: 74468

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0621 Hom.: 251

Bravo AF: 0.0987

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs6602391; hg19: chr10-6078032;