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NM_000074.3(CD40LG):c.156+1G>A AND Hyper-IgM syndrome type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 2022
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:
RCV003066380.3

Allele description [Variation Report for NM_000074.3(CD40LG):c.156+1G>A]

NM_000074.3(CD40LG):c.156+1G>A

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.156+1G>A
HGVS:
  • NC_000023.11:g.136648405G>A
  • NG_007280.1:g.5229G>A
  • NM_000074.3:c.156+1G>AMANE SELECT
  • LRG_141:g.5229G>A
  • NC_000023.10:g.135730564G>A
Molecular consequence:
  • NM_000074.3:c.156+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003445783Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 1, 2022) 		germlineclinical testing

PubMed (6)
[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

Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome.

Lee WI, Torgerson TR, Schumacher MJ, Yel L, Zhu Q, Ochs HD.

Blood. 2005 Mar 1;105(5):1881-90. Epub 2004 Sep 9.

PubMed [citation]
PMID:
15358621

Clinical and laboratory findings in hyper-IgM syndrome with novel CD40L and AICDA mutations.

Aghamohammadi A, Parvaneh N, Rezaei N, Moazzami K, Kashef S, Abolhassani H, Imanzadeh A, Mohammadi J, Hammarström L.

J Clin Immunol. 2009 Nov;29(6):769-76. doi: 10.1007/s10875-009-9315-7. Epub 2009 Jul 3.

PubMed [citation]
PMID:
19575287
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003445783.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individuals with hyper IgM syndrome (PMID: 15358621, 19575287, 31117086). This variant is present in population databases (rs144855738, gnomAD 0.003%). This sequence change affects a donor splice site in intron 1 of the CD40LG 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 CD40LG are known to be pathogenic (PMID: 15319456).

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

Last Updated: Sep 29, 2024