NM_000417.3(IL2RA):c.583+2T>C AND Immunodeficiency due to CD25 deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002040509.3

Allele description [Variation Report for NM_000417.3(IL2RA):c.583+2T>C]

NM_000417.3(IL2RA):c.583+2T>C

Gene:

IL2RA:interleukin 2 receptor subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p15.1

Genomic location:

Preferred name:

NM_000417.3(IL2RA):c.583+2T>C

HGVS:

NC_000010.11:g.6021476A>G
NG_007403.1:g.45834T>C
NM_000417.3:c.583+2T>CMANE SELECT
NM_001308242.2:c.368-1535T>C
NM_001308243.2:c.368-1977T>C
LRG_73:g.45834T>C
NC_000010.10:g.6063439A>G

Links:

dbSNP: rs2132853537

NCBI 1000 Genomes Browser:

rs2132853537

Molecular consequence:

NM_001308242.2:c.368-1535T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001308243.2:c.368-1977T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000417.3:c.583+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Immunodeficiency due to CD25 deficiency
Synonyms:: CD25 DEFICIENCY; IL2RA DEFICIENCY; Interleukin 2 receptor, alpha, deficiency of; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011664; MedGen: C1853392; Orphanet: 169100; OMIM: 606367

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002297699	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 9096364, 17196245, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002297699

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 15, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor.

Sharfe N, Dadi HK, Shahar M, Roifman CM.

Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3168-71.

PubMed [citation]

PMID:: 9096364
PMCID:: PMC20340

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002297699.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

ClinVar contains an entry for this variant (Variation ID: 1508767). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with IL2RA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 4 of the IL2RA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IL2RA are known to be pathogenic (PMID: 9096364, 17196245).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

ClinVar

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