NM_001250.6(CD40):c.157G>T (p.Glu53Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 21, 2023
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:: RCV002848000.3

Allele description [Variation Report for NM_001250.6(CD40):c.157G>T (p.Glu53Ter)]

NM_001250.6(CD40):c.157G>T (p.Glu53Ter)

Gene:

CD40:CD40 molecule [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_001250.6(CD40):c.157G>T (p.Glu53Ter)

HGVS:

NC_000020.11:g.46122259G>T
NG_007279.1:g.8993G>T
NM_001250.6:c.157G>TMANE SELECT
NM_001302753.2:c.157G>T
NM_001322421.2:c.157G>T
NM_001322422.2:c.157G>T
NM_001362758.2:c.157G>T
NM_152854.4:c.157G>T
NP_001241.1:p.Glu53Ter
NP_001241.1:p.Glu53Ter
NP_001289682.1:p.Glu53Ter
NP_001309350.1:p.Glu53Ter
NP_001309351.1:p.Glu53Ter
NP_001349687.1:p.Glu53Ter
NP_690593.1:p.Glu53Ter
LRG_40t1:c.157G>T
LRG_40:g.8993G>T
LRG_40p1:p.Glu53Ter
NC_000020.10:g.44750898G>T
NM_001250.4:c.157G>T
NR_126502.2:n.187G>T
NR_136327.2:n.187G>T

Protein change:

E53*

Molecular consequence:

NR_126502.2:n.187G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_136327.2:n.187G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001250.6:c.157G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001302753.2:c.157G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322421.2:c.157G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322422.2:c.157G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001362758.2:c.157G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_152854.4:c.157G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003226484	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 21, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20702779, 24122029, 35729272, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003226484

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 21, 2023)

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

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

Clinical, immunological, and molecular characterization of hyper-IgM syndrome due to CD40 deficiency in eleven patients.

Al-Saud BK, Al-Sum Z, Alassiri H, Al-Ghonaium A, Al-Muhsen S, Al-Dhekri H, Arnaout R, Alsmadi O, Borrero E, Abu-Staiteh A, Rawas F, Al-Mousa H, Hawwari A.

J Clin Immunol. 2013 Nov;33(8):1325-35. Review.

PubMed [citation]

PMID:: 24122029

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003226484.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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. ClinVar contains an entry for this variant (Variation ID: 2024847). This variant has not been reported in the literature in individuals affected with CD40-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu53*) in the CD40 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CD40 are known to be pathogenic (PMID: 20702779, 24122029, 35729272).

#	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: Sep 29, 2024

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