COVID-19 research

Gene: CARD14

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

I don't know

Green List (high evidence)

Psoriasis ?relevant phenotype (also some evidence of presence in controls - is it useful clinically?

Created: 26 Sep 2019, 3:50 p.m. | Last Modified: 26 Sep 2019, 3:50 p.m.

Panel Version: 1.130

Comment on list classification: Changed rating from Amber to Green. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June (North West GLH) and 6th September (LNGLH). The Specialist Test Group all agreed that there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 4:44 p.m. | Last Modified: 17 Sep 2019, 4:44 p.m.

Panel Version: 1.95

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Review suggest from Tracy Briggs on behalf of North West GLH notes that Somatic mutations cause Ras-associated autoimmune leukoproliferative disorder (RALD)

Created: 12 Sep 2019, 3 p.m. | Last Modified: 12 Sep 2019, 3 p.m.

Panel Version: 1.55

Comment on publications: Added publications 30248356; 29980436 suggested by Kimberly Gilmour (London North GLH) on behalf of The Specialist Test Group to support inclusion of this gene on the panel to support Green review. This gene needs discussing with The Immunology Specialist Test Group in view of dermatological presentation rather than immunological

Created: 12 Sep 2019, 2:57 p.m. | Last Modified: 12 Sep 2019, 2:57 p.m.

Panel Version: 1.55

Additional external review added so this gene was reviewed again. Pathogenic variants in CARD14 results in a monogenic autoinflammatory disease, however the the clinical manifestation is dermatological rather than immunological presentation. This gene will remain as Amber on this panel, as it is rated Green on the generalised pustular psoriasis panel

Created: 21 Sep 2018, 11:42 a.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CARD14 .PanelApp HGNC gene symbol check: CARD14 . IUIS Disease: CAMPS (CARD14 mediated psoriasis) . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: Mainly in keratinocytes. IUIS Associated features: Psoriasis. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Non-Inflammasome Related Conditions

Created: 2 Jul 2018, 10:35 a.m.

Comment on list classification: demoted from Green to Amber after clinical review. This is more of a dermatological presentation rather than immunological. In view of the number of cases with psoriasis, this gene should be Green on the generalised pustular psoriasis panel.

Created: 29 Jun 2018, 5:31 p.m.

Comment on list classification: Added publications to support upgrading of the gene to Green, there are more than 3 unrelated cases, plus mouse model. Gene also listed on diagnostic panels, Victorian Clinical Genetics Services and GRID.

Created: 27 Jun 2018, 1:37 p.m.

Comment on publications: PMID: 29689250 reported that heterozygous mice harboring a CARD14 gain-of-function mutation spontaneously develop a chronic psoriatic phenotype with characteristic scaling skin lesions, epidermal thickening, keratinocyte hyperproliferation, hyperkeratosis and immune cell infiltration.

Created: 27 Jun 2018, 1:34 p.m.

Spoerri et al. (2018) PMID: 29704870 Psoriasis susceptibility (PSORS)2 and pityriasis rubra pilaris (PRP) are both monogenic autoinflammatory diseases. Both phenotypes have been associated to CARD14 variants (PMID:23648549;22521418; 22703878; 2306708). CARD14 is an epidermal regulator of NF-κB transcription factor, variants in CARD14 initiate a process that includes inflammatory cell recruitment by keratinocytes and perpetuate a vicious cycle of epidermal inflammation and regeneration that cause the abnormal keratinization. c.349G > A, p.Gly117Ser is the the most prevalent variant, and c.413A > C, p.Glu138Ala (a de novo mutation) were shown to lead to enhanced NF-kB activation and upregulation of a subset of psoriasis-associated genes in keratinocytes (PMID:22521418).

Created: 27 Jun 2018, 1:24 p.m.

Comment on publications: added publications to support phenotype

Created: 27 Jun 2018, 1:08 p.m.

The most prevalent pathogenic variant is c.349G>A, p.Gly117Ser, which has been reported in a number of unrelated families and ethnicities PMID:23648549;22521418; 22703878; 2306708.

Created: 27 Jun 2018, 12:15 p.m.

Although most of the cases of Psoriasis are sporadic and acquired, a familial form of the disease exists. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression. Psoriasis is a chronic immune-mediated inflammatory disease of the skin, this panel includes Autoinflammatory disorders.

Created: 27 Jun 2018, 11:04 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: CAD14, PanelApp HGNC gene symbol check: CARD14, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Autoinflammatory disorders / Other autoinflammatory diseases with known genetic defect / Other autoinflammatory diseases with known genetic defect

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CARD14, GRID_Gene_Symbol: CARD14, GRID_Transcript_ENS_Community submitted: ENST00000344227, GRID_Transcript_RefSeq: NM_024110.4, GRID_Transcript_ENS_used_on_Production: ENST00000344227

Created: 17 Apr 2018, 12:12 p.m.