NM_002185.5(IL7R):c.616C>T (p.Arg206Ter) AND T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 8, 2024
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:: RCV004017858.1

Allele description [Variation Report for NM_002185.5(IL7R):c.616C>T (p.Arg206Ter)]

NM_002185.5(IL7R):c.616C>T (p.Arg206Ter)

Gene:

IL7R:interleukin 7 receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p13.2

Genomic location:

Preferred name:

NM_002185.5(IL7R):c.616C>T (p.Arg206Ter)

Other names:

NM_002185.5(IL7R):c.616C>T; p.Arg206Ter

HGVS:

NC_000005.10:g.35873558C>T
NG_009567.1:g.21670C>T
NM_002185.5:c.616C>TMANE SELECT
NP_002176.2:p.Arg206Ter
LRG_74:g.21670C>T
NC_000005.9:g.35873660C>T
NM_002185.2:c.616C>T

Protein change:

R206*

Links:

dbSNP: rs201559094

NCBI 1000 Genomes Browser:

rs201559094

Molecular consequence:

NM_002185.5:c.616C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency
Identifiers:: MONDO: MONDO:0015701; MedGen: C5679577

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004847488	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 8, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15615257, 20021794, 28747913, 32445296, 33628209, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004847488

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 8, 2024)

germline

clinical testing

PubMed (6)
[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

Characterization of a novel nonsense mutation in the interleukin-7 receptor alpha gene in a Korean patient with severe combined immunodeficiency.

Jo EK, Kook H, Uchiyama T, Hakozaki I, Kim YO, Song CH, Park JK, Kanegane H, Tsuchiya S, Kumaki S.

Int J Hematol. 2004 Nov;80(4):332-5.

PubMed [citation]

PMID:: 15615257

[A compound heterozygosity mutation in the interleukin-7 receptor-alpha gene resulted in severe combined immunodeficiency in a Chinese patient].

Zhang ZY, Zhao XD, Wang M, Yu J, An YF, Yang XQ.

Zhonghua Er Ke Za Zhi. 2009 Sep;47(9):691-5. Chinese.

PubMed [citation]

PMID:: 20021794

See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847488.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.Arg206X variant in IL7R has been reported in homozygous state in at least 4 individuals and in the compound heterozygous state (confirmed in trans) with another disease-causing variant in IL7RA in 1 individual with IL7R-associated severe combined immunodeficiency (SCID; Jo 2004 PMID: 15615257, Zhang 2009 PMID: 20021794, Luk 2017 PMID: 28747913, Firtina 2020 PMID: 32445296, Vignesh 2021 PMID: 33628209). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 1298987) and has been identified in 0.007% (4/60022) of Latino/Admixed American chromosomes by gnomAD (http://gnomad.broadinstitute.org, v4.0.0), consistent with a recessive allele frequency. This nonsense variant leads to a premature termination codon at position 206, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the IL7R gene is an established disease mechanism in autosomal recessive IL7R-associated SCID. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive IL7R-associated SCID. ACMG/AMP Criteria applied: PVS1, PM3, PM2_Supporting.

#	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: Oct 20, 2024

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