chr10-6035833-T-C

Variant names:

• chr10-6035833-T-C
• rs7910961
• NM_000417.3:c.65-9808A>G

Variant summary

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

The NM_000417.3(IL2RA):​c.65-9808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,212 control chromosomes in the GnomAD database, including 39,546 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 0.71 (39534 hom., cov: 32)
  • Exomes 𝑓: 0.64 (12 hom.)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 20 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

IL2RA-AS1 (HGNC:58167):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 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.65-9808A>G		intron	N/A	NP_000408.1	P01589
	IL2RA	NM_001308242.2		c.65-9808A>G		intron	N/A	NP_001295171.1	Q5W005
	IL2RA	NM_001308243.2		c.65-9808A>G		intron	N/A	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.65-9808A>G		intron	N/A	ENSP00000369293.3	P01589
	IL2RA	ENST00000379954.5	TSL:1	c.65-9808A>G		intron	N/A	ENSP00000369287.1	Q5W005
	IL2RA	ENST00000447847.2	TSL:1	c.65-9808A>G		intron	N/A	ENSP00000402024.2	H0Y5Z0

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108593 AN: 152036 Hom.: 39487 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.677

GnomAD4 exome AF: 0.643 AC: 36 AN: 56 Hom.: 12 AF XY: 0.682 AC XY: 30 AN XY: 44

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.650 AC: 26 AN: 40

Other (OTH) AF: 0.625 AC: 5 AN: 8

GnomAD4 genome AF: 0.714 AC: 108697 AN: 152156 Hom.: 39534 Cov.: 32 AF XY: 0.715 AC XY: 53197 AN XY: 74382

African (AFR) AF: 0.828 AC: 34361 AN: 41510

American (AMR) AF: 0.609 AC: 9300 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2192 AN: 3466

East Asian (EAS) AF: 0.927 AC: 4802 AN: 5182

South Asian (SAS) AF: 0.811 AC: 3910 AN: 4824

European-Finnish (FIN) AF: 0.658 AC: 6957 AN: 10576

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44898 AN: 67996

Other (OTH) AF: 0.682 AC: 1441 AN: 2114

Alfa AF: 0.675 Hom.: 109939

Bravo AF: 0.708

Asia WGS AF: 0.854 AC: 2971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.19
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: rs7910961; hg19: chr10-6077796;