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Primary immunodeficiency

Gene: CD8A

Amber List (moderate evidence)

CD8A (CD8a molecule)
EnsemblGeneIds (GRCh38): ENSG00000153563
EnsemblGeneIds (GRCh37): ENSG00000153563
OMIM: 186910, Gene2Phenotype
CD8A is in 3 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Changed rating of gene from Red to Amber. This gene was rated as Amber in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.
Created: 14 Oct 2020, 12:12 p.m. | Last Modified: 14 Oct 2020, 12:12 p.m.
Panel Version: 2.211
The following PubMed IDs were added to gene CD8A (OMIM gene MIM#186910): 17658607;26563160;11435463. These publications have been associated with the gene by the immunodeficiencies subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.
Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208

Publications

Sophie Hambleton (Newcastle University)

I don't know

Louise Daugherty (Genomics England Curator)

I don't know

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CD8A .PanelApp HGNC gene symbol check: CD8A . IUIS Disease: CD8 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent infections, may be asymptomatic. IUIS Major category: Immunodeficiencies affecting cellular and humoral immunity. IUIS Subcategory: Combined Immunodeficiencies Generally Less Profound than Severe Combined Immunodeficiency
Created: 2 Jul 2018, 10:35 a.m.
Keep amber after external expert review until more info on gene and disease association
Created: 27 Jun 2018, 7:13 p.m.
Kept Amber to Green after internal clinical review, it was noted that there is a single variant in a single population without any functional work up to support this variant or the mechanism. Feeding back all rare variants in this gene currently would not seem to beneficial, in particular when the Immunologists would be able to identify isolated CD8+ lymphocyte deficiency through their work up (T cell subset testing). Keep Amber until further evidence on gene/variants.
Created: 15 Jun 2018, 9:50 a.m.
Past onto clinical team for further discussion. Our current PanelApp rules denote that for a founder mutation we cannot make these genes Green. There are exceptions to this rule (reviewed by clinical team) if there has been an additional pathogenic var. conformed/reported. In this instance there is currently only one mutation that gives rise to observed PID phenotype.
Created: 11 Jun 2018, 2:19 p.m.
added founder -effect tag
Created: 11 Jun 2018, noon
Comment on publications: de la Calle-Martin et al. (2001) PMID: 11435463 described a patient of Spanish-gyypsy origin with recurrent bacterial and viral infections and total absence of CD8-positive T cells, and identified a homozygous 331G-A transition in the CD8A gene, resulting in a gly90-to-ser (G90S) substitution in a conserved residue in the immunoglobulin domain of the protein.
Mancebo E et al. (2008) PMID:17658607 describes the second case for CD8 immunodeficiency confirming the pathogenic effect of p.Gly111Ser, the same variant as previously reported by de la Calle-Martin et al. (2001). Looking at 1127 unrelated control individuals: 734 subjects of Gypsy ancestry from different sub-isolates and geographic locations in Europe, and 393 of Spanish (non-Gypsy) ethnicity. The result indicated that p.Gly111Ser is confined to the Spanish Gypsy population, where it occurs at a carrier rate of 0.4%. Analysis of microsatellite markers flanking the CD8A mutated gene revealed a shared polymorphic haplotype suggesting a common founder for p.Gly111Ser mutation that causes CD8 deficiency in the Spanish Gypsy population. CD8 immunodeficiency should be given diagnostic consideration in Spanish Gypsies with recurrent infections.
Created: 11 Jun 2018, 11:49 a.m.
Comment on phenotypes: added phenotype from Orphanet and OMIN MIMid. Susceptibility to respiratory infections associated with CD8 alpha chain mutation is a rare primary immunodeficiency due to a defect in adaptive immunity characterized by the absence of CD8+ T cells with normal immunoglobulin and specific antibody titres in blood and susceptibility to recurrent respiratory bacterial and viral infections. Symptom severity range from fatal respiratory insufficiency to mild or asymptomatic phenotypes.
Created: 11 Jun 2018, 10:27 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.
Created: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: CD8A, PanelApp HGNC gene symbol check: CD8A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / CD8-deficiency / CD8 deficiency
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CD8A, GRID_Gene_Symbol: CD8A, GRID_Transcript_ENS_Community submitted: ENST00000409511, GRID_Transcript_RefSeq: NM_001768.6, GRID_Transcript_ENS_used_on_Production: ENST00000409511
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
  • IUIS Classification December 2019
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • CD8 deficiency familial, 608957
  • Susceptibility to respiratory infections associated with CD8alpha chain mutation
  • Recurrent infections, may be asymptomatic
  • Immunodeficiencies affecting cellular and humoral immunity
Tags
founder-effect
OMIM
186910
Clinvar variants
Variants in CD8A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: cd8a has been classified as Amber List (Moderate Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications, Status Update

Eleanor Williams (Genomics England Curator)

Source Other was added to CD8A. Publications for gene CD8A were updated from 32048120; 17658607; 11435463; 32086639 to 32048120; 32086639; 26563160; 17658607; 11435463 Rating Changed from Amber List (moderate evidence) to Red List (low evidence)

28 Feb 2020, Gel status: 2

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Source IUIS Classification December 2019 was added to CD8A. Added phenotypes Recurrent infections, may be asymptomatic; Immunodeficiencies affecting cellular and humoral immunity for gene: CD8A Publications for gene CD8A were updated from 11435463; 17658607 to 32048120; 17658607; 11435463; 32086639

12 Jul 2018, Gel status: 2

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene CD8A were set to CD8 deficiency familial, 608957, Susceptibility to respiratory infections associated with CD8alpha chain mutation, Recurrent infections, may be asymptomatic, Immunodeficiencies affecting cellular and humoral immunity

27 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: cd8a has been classified as Amber List (Moderate Evidence).

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to CD8A. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to CD8A. Panel: Primary immunodeficiency disorders

15 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: cd8a has been classified as Amber List (Moderate Evidence).

11 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: CD8A were set to 11435463; 17658607

11 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: CD8A were set to CD8 deficiency familial, 608957; Susceptibility to respiratory infections associated with CD8alpha chain mutation

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to CD8A. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to CD8A. Panel: Primary immunodeficiency disorders Phenotypes for gene CD8A were set to CD8 deficiency

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene CD8A were set to CD8 deficiency

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

CD8A was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

CD8A was created by Louise Daugherty