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NM_000074.3(CD40LG):c.770G>A (p.Gly257Asp) AND Hyper-IgM syndrome type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 25, 2020
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:
RCV001237589.7

Allele description [Variation Report for NM_000074.3(CD40LG):c.770G>A (p.Gly257Asp)]

NM_000074.3(CD40LG):c.770G>A (p.Gly257Asp)

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.770G>A (p.Gly257Asp)
HGVS:
  • NC_000023.11:g.136659399G>A
  • NG_007280.1:g.16223G>A
  • NM_000074.3:c.770G>AMANE SELECT
  • NP_000065.1:p.Gly257Asp
  • LRG_141t1:c.770G>A
  • LRG_141:g.16223G>A
  • NC_000023.10:g.135741558G>A
  • NM_000074.2:c.770G>A
Protein change:
G257D
Links:
dbSNP: rs1477466218
NCBI 1000 Genomes Browser:
rs1477466218
Molecular consequence:
  • NM_000074.3:c.770G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001410355Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 25, 2020) 		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

Pitfalls of "hyper"-IgM syndrome: a new CD40 ligand mutation in the presence of low IgM levels. A case report and a critical review of the literature.

Heinold A, Hanebeck B, Daniel V, Heyder J, Tran TH, Döhler B, Greil J, Müller FM.

Infection. 2010 Dec;38(6):491-6. doi: 10.1007/s15010-010-0061-9. Epub 2010 Oct 28. Review.

PubMed [citation]
PMID:
20981468

Mutation analysis in CD40 ligand deficiency leading to X-linked hypogammaglobulinemia with hyper IgM syndrome.

Katz F, Hinshelwood S, Rutland P, Jones A, Kinnon C, Morgan G.

Hum Mutat. 1996;8(3):223-8.

PubMed [citation]
PMID:
8889581
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001410355.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly257 amino acid residue in CD40LG. Other variant(s) that disrupt this residue have been observed in individuals with CD40LG-related conditions (PMID: 20981468, 8889581), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual affected with hyper-IgM syndrome (PMID: 10366125). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 257 of the CD40LG protein (p.Gly257Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.

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

Last Updated: Apr 6, 2024