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NM_000733.4(CD3E):c.49+1G>A AND Immunodeficiency 18

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 28, 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:
RCV003745739.2

Allele description [Variation Report for NM_000733.4(CD3E):c.49+1G>A]

NM_000733.4(CD3E):c.49+1G>A

Gene:
CD3E:CD3 epsilon subunit of T-cell receptor complex [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.3
Genomic location:
Preferred name:
NM_000733.4(CD3E):c.49+1G>A
HGVS:
  • NC_000011.10:g.118305002G>A
  • NG_007383.1:g.5423G>A
  • NM_000733.4:c.49+1G>AMANE SELECT
  • LRG_38:g.5423G>A
  • NC_000011.9:g.118175717G>A
Molecular consequence:
  • NM_000733.4:c.49+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Immunodeficiency 18 (IMD18)
Synonyms:
CD3-EPSILON DEFICIENCY; CD3epsilon deficiency
Identifiers:
MONDO: MONDO:0014278; MedGen: C3810127; OMIM: 615615

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004382233Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 28, 2023) 		germlineclinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Independent mutations of the human CD3-epsilon gene resulting in a T cell receptor/CD3 complex immunodeficiency.

Soudais C, de Villartay JP, Le Deist F, Fischer A, Lisowska-Grospierre B.

Nat Genet. 1993 Jan;3(1):77-81.

PubMed [citation]
PMID:
8490660
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004382233.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change affects a donor splice site in intron 2 of the CD3E 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 CD3E are known to be pathogenic (PMID: 8490660, 15546002). This variant is not present in population databases (gnomAD no frequency). 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. Studies have shown that disruption of this splice site alters CD3E gene expression (PMID: 24515816). Disruption of this splice site has been observed in individual(s) with severe combined immunodeficiency due to CD3-epsilon deficiency (PMID: 24515816).

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

Last Updated: Sep 29, 2024