NM_001250.6(CD40):c.95TAA[1] (p.Ile33del) AND Hyper-IgM syndrome type 3

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 23, 2010
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:: RCV000022450.29

Allele description [Variation Report for NM_001250.6(CD40):c.95TAA[1] (p.Ile33del)]

NM_001250.6(CD40):c.95TAA[1] (p.Ile33del)

Gene:

CD40:CD40 molecule [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_001250.6(CD40):c.95TAA[1] (p.Ile33del)

HGVS:

NC_000020.11:g.46121863TAA[1]
NG_007279.1:g.8597TAA[1]
NM_001250.6:c.95TAA[1]MANE SELECT
NM_001302753.2:c.95TAA[1]
NM_001322421.2:c.95TAA[1]
NM_001322422.2:c.95TAA[1]
NM_001362758.2:c.95TAA[1]
NM_152854.4:c.95TAA[1]
NP_001241.1:p.Ile33del
NP_001289682.1:p.Ile33del
NP_001309350.1:p.Ile33del
NP_001309351.1:p.Ile33del
NP_001349687.1:p.Ile33del
NP_690593.1:p.Ile33del
LRG_40:g.8597TAA[1]
NC_000020.10:g.44750502TAA[1]
NM_001250.5:c.98_100delTAA
NR_126502.2:n.125TAA[1]
NR_136327.2:n.125TAA[1]

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

I33del

Links:

OMIM: 109535.0004; dbSNP: rs1568905451

NCBI 1000 Genomes Browser:

rs1568905451

Molecular consequence:

NM_001250.6:c.95TAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001302753.2:c.95TAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001322421.2:c.95TAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001322422.2:c.95TAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001362758.2:c.95TAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_152854.4:c.95TAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_126502.2:n.125TAA[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_136327.2:n.125TAA[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hyper-IgM syndrome type 3
Synonyms:: Immunodeficiency with hyper IgM type 3; Hyper-IgM Immunodeficiency Syndrome, Type 3
Identifiers:: MONDO: MONDO:0011735; MedGen: C1720957; OMIM: 606843

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000043739	OMIM	no assertion criteria provided	Pathogenic (Dec 23, 2010)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 17502893, 20702779

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000043739

OMIM

no assertion criteria provided

Pathogenic
(Dec 23, 2010)

germline

literature only

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

First report of successful stem cell transplantation in a child with CD40 deficiency.

Mazzolari E, Lanzi G, Forino C, Lanfranchi A, Aksu G, Ozturk C, Giliani S, Notarangelo LD, Kutukculer N.

Bone Marrow Transplant. 2007 Aug;40(3):279-81. Epub 2007 May 14. No abstract available.

PubMed [citation]

PMID:: 17502893

Different molecular behavior of CD40 mutants causing hyper-IgM syndrome.

Lanzi G, Ferrari S, Vihinen M, Caraffi S, Kutukculer N, Schiaffonati L, Plebani A, Notarangelo LD, Fra AM, Giliani S.

Blood. 2010 Dec 23;116(26):5867-74. doi: 10.1182/blood-2010-03-274241. Epub 2010 Aug 11.

PubMed [citation]

PMID:: 20702779

Details of each submission

From OMIM, SCV000043739.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a 2-year-old Turkish girl, born of consanguineous parents, with immunodeficiency with hyper-IgM (HIGM3; 606843), Mazzolari et al. (2007) identified a homozygous 3-bp deletion (175delTAA) in exon 2 of the CD40 gene, resulting in the deletion of residue ile33 (I33del) in the extracellular domain. She underwent successful bone marrow transplantation at age 3, resulting in stable multilineage full chimerism and normal immune function.

By in vitro studies, Lanzi et al. (2010) showed that most of the I33del-mutant protein was retained in the endoplasmic reticulum, although a small fraction of the mutant protein reached the cell surface, where it was competent for signaling.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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