10-6019818-T-C

Position:

• chr10-6019818-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000417.3(IL2RA):​c.655+52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,533,098 control chromosomes in the GnomAD database, including 619,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.86 (56906 hom., cov: 32)
  • Exomes 𝑓: 0.90 (562257 hom.)
• Consequence: IL2RA NM_000417.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0510

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-6019818-T-C is Benign according to our data. Variant chr10-6019818-T-C is described in ClinVar as [Benign]. Clinvar id is 2628287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL2RA	NM_000417.3	c.655+52A>G		intron_variant		ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2	c.439+52A>G		intron_variant			NP_001295171.1
IL2RA	NM_001308243.2	c.368-319A>G		intron_variant			NP_001295172.1
LOC124902368	XR_007062042.1	n.144-1518T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8	c.655+52A>G		intron_variant		1	NM_000417.3	ENSP00000369293.3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131030 AN: 152034 Hom.: 56856 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.873

GnomAD4 exome AF: 0.900 AC: 1243023 AN: 1380946 Hom.: 562257 Cov.: 21 AF XY: 0.900 AC XY: 622453 AN XY: 691396

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.929

Gnomad4 EAS exome AF: 0.772

Gnomad4 SAS exome AF: 0.861

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.925

Gnomad4 OTH exome AF: 0.890

GnomAD4 genome AF: 0.862 AC: 131128 AN: 152152 Hom.: 56906 Cov.: 32 AF XY: 0.854 AC XY: 63517 AN XY: 74358

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.926

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.923

Gnomad4 OTH AF: 0.869

Alfa AF: 0.893 Hom.: 7986

Bravo AF: 0.851

Asia WGS AF: 0.784 AC: 2728 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 85. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.35

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: rs10752175; hg19: chr10-6061781;