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NM_000074.3(CD40LG):c.694C>T (p.Gln232Ter) AND Hyper-IgM syndrome type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 5, 2019
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:
RCV001203125.9

Allele description [Variation Report for NM_000074.3(CD40LG):c.694C>T (p.Gln232Ter)]

NM_000074.3(CD40LG):c.694C>T (p.Gln232Ter)

Gene:
CD40LG:CD40 ligand [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq26.3
Genomic location:
Preferred name:
NM_000074.3(CD40LG):c.694C>T (p.Gln232Ter)
HGVS:
  • NC_000023.11:g.136659323C>T
  • NG_007280.1:g.16147C>T
  • NM_000074.3:c.694C>TMANE SELECT
  • NP_000065.1:p.Gln232Ter
  • LRG_141t1:c.694C>T
  • LRG_141:g.16147C>T
  • NC_000023.10:g.135741482C>T
  • NM_000074.2:c.694C>T
Protein change:
Q232*
Links:
dbSNP: rs2076127875
NCBI 1000 Genomes Browser:
rs2076127875
Molecular consequence:
  • NM_000074.3:c.694C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hyper-IgM syndrome type 1
Synonyms:
Immunodeficiency with hyper IgM type 1; Hyper IgM immunodeficiency, X-linked; Hyper-IgM Immunodeficiency Syndrome, Type 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010626; MedGen: C0398689; OMIM: 308230

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001374272Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 5, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans.

Weller S, Faili A, Garcia C, Braun MC, Le Deist F F, de Saint Basile G G, Hermine O, Fischer A, Reynaud CA, Weill JC.

Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1166-70.

PubMed [citation]
PMID:
11158612
PMCID:
PMC14726

A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome.

Lin Q, Rohrer J, Allen RC, Larché M, Greene JM, Shigeoka AO, Gatti RA, Derauf DC, Belmont JW, Conley ME.

J Clin Invest. 1996 Jan 1;97(1):196-201.

PubMed [citation]
PMID:
8550833
PMCID:
PMC507079
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001374272.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This variant disrupts the C-terminus of the CD40LG protein. Other variant(s) that disrupt this region (p.Ser236*) have been observed in individuals with CD40LG-related conditions (PMID: 11158612). This suggests that this may be a clinically significant region of the protein. This sequence change results in a premature translational stop signal in the CD40LG gene (p.Gln232*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 30 amino acids of the CD40LG protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with X-linked Hyper-IgM Immunodeficiency (PMID: 8550833, 18805740). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024