rs10905656

Variant names:

• chr10-6044130-C-A
• rs10905656
• NM_000417.3:c.64+17958G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-6044130-C-A
• chr10-6044130-C-G
• chr10-6044130-C-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.64+17958G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,096 control chromosomes in the GnomAD database, including 12,877 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 0.39 (12877 hom., cov: 33)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565
• Publications: 14 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RA	NM_000417.3	c.64+17958G>T		intron_variant	Intron 1 of 7	ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2	c.64+17958G>T		intron_variant	Intron 1 of 6		NP_001295171.1
IL2RA	NM_001308243.2	c.64+17958G>T		intron_variant	Intron 1 of 5		NP_001295172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8	c.64+17958G>T		intron_variant	Intron 1 of 7	1	NM_000417.3	ENSP00000369293.3

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59665 AN: 151978 Hom.: 12859 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.393 AC: 59710 AN: 152096 Hom.: 12877 Cov.: 33 AF XY: 0.402 AC XY: 29914 AN XY: 74352

African (AFR) AF: 0.231 AC: 9605 AN: 41500

American (AMR) AF: 0.552 AC: 8437 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3472

East Asian (EAS) AF: 0.610 AC: 3151 AN: 5164

South Asian (SAS) AF: 0.423 AC: 2039 AN: 4818

European-Finnish (FIN) AF: 0.516 AC: 5456 AN: 10564

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28155 AN: 67986

Other (OTH) AF: 0.418 AC: 883 AN: 2112

Alfa AF: 0.411 Hom.: 20182

Bravo AF: 0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.76
PhyloP100		0.56
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: rs10905656; hg19: chr10-6086093;