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NM_000565.4(IL6R):c.548del (p.Gly183fs) AND Hyper-IgE recurrent infection syndrome 5, autosomal recessive

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 5, 2023
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001250128.2

Allele description [Variation Report for NM_000565.4(IL6R):c.548del (p.Gly183fs)]

NM_000565.4(IL6R):c.548del (p.Gly183fs)

Gene:
IL6R:interleukin 6 receptor [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1q21.3
Genomic location:
Preferred name:
NM_000565.4(IL6R):c.548del (p.Gly183fs)
HGVS:
  • NC_000001.11:g.154434608del
  • NG_012087.1:g.34416del
  • NM_000565.4:c.548delMANE SELECT
  • NM_001206866.2:c.548del
  • NM_001382769.1:c.548del
  • NM_001382770.1:c.548del
  • NM_001382771.1:c.548del
  • NM_001382772.1:c.548del
  • NM_001382773.1:c.548del
  • NM_001382774.1:c.188del
  • NM_181359.3:c.548del
  • NP_000556.1:p.Gly183fs
  • NP_001193795.1:p.Gly183fs
  • NP_001369698.1:p.Gly183fs
  • NP_001369699.1:p.Gly183fs
  • NP_001369700.1:p.Gly183fs
  • NP_001369701.1:p.Gly183fs
  • NP_001369702.1:p.Gly183fs
  • NP_001369703.1:p.Gly63fs
  • NP_852004.1:p.Gly183fs
  • NC_000001.10:g.154407084del
  • NM_000565.3:c.548delG
Protein change:
G183fs
Links:
OMIM: 147880.0002; dbSNP: rs1689501445
NCBI 1000 Genomes Browser:
rs1689501445
Molecular consequence:
  • NM_000565.4:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001206866.2:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001382769.1:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001382770.1:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001382771.1:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001382772.1:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001382773.1:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001382774.1:c.188del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181359.3:c.548del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hyper-IgE recurrent infection syndrome 5, autosomal recessive
Synonyms:
HYPER-IgE SYNDROME 5, AUTOSOMAL RECESSIVE, WITH RECURRENT INFECTIONS
Identifiers:
MONDO: MONDO:0030069; MedGen: C5394550; OMIM: 618944

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001424529OMIM
no assertion criteria provided
Pathogenic
(Oct 5, 2023) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses.

Spencer S, Köstel Bal S, Egner W, Lango Allen H, Raza SI, Ma CA, Gürel M, Zhang Y, Sun G, Sabroe RA, Greene D, Rae W, Shahin T, Kania K, Ardy RC, Thian M, Staples E, Pecchia-Bekkum A, Worrall WPM, Stephens J, Brown M, Tuna S, et al.

J Exp Med. 2019 Sep 2;216(9):1986-1998. doi: 10.1084/jem.20190344. Epub 2019 Jun 24.

PubMed [citation]
PMID:
31235509
PMCID:
PMC6719421

Details of each submission

From OMIM, SCV001424529.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a woman (P1), born of unrelated English parents, with autosomal recessive hyper-IgE syndrome-5 with recurrent infections (HIES5; 618944), Spencer et al. (2019) identified a homozygous 1-bp deletion (c.548delG, NM_000565.3) in exon 4 of the IL6R gene, resulting in a frameshift and premature termination (Gly183Glufs7) in the cytokine-binding domain. The mutation, which was found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the gnomAD database. Patient T cells showed reduced IL6R surface expression and absent IL6 (147620)-mediated phosphorylation of STAT1 (600555) and STAT3 (102582), consistent with a loss of function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 14, 2023