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:: RCV001203125.8

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001374272	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 5, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11158612, 8550833, 18805740, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001374272

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 5, 2019)

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

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 Invitae, SCV001374272.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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: Jun 23, 2024

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