Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: F12
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
NB allelic AR disorder of factor XII deficiency produces Hageman traitCreated: 29 Jun 2018, 1:53 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hereditary angioedema
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
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
The missense variants NG_007568.1(NM_000505.3):c.983C>A;p.Thr328Lys and NG_007568.1(NM_000505.3):c.983C>G;p.Thr328Arg affect the threonine residue at position 328 of the protein.1, 2 The p.Thr328Lys variant accounts for the large majority of variant-positive cases reported to date. p.Thr328Lys has been described in patients/families from various ethnic backgrounds. In addition to the two missense variants, one deletion and one duplication have been reported in single families. The NG_007568.1(NM_000505.3):c.971_1018+24del;p.Lys324_Ala340delinsThr variant is a deletion of 72 base pairs (bp). As with the missense variants, the duplication and the deletion affect the proline-rich regionCreated: 3 Jul 2018, 11:29 a.m.
Comment on list classification: Changed Amber to Green from external expert review and further publications to support gene-disease association. To date, four disease-causing variants in F12 have been reported .Created: 3 Jul 2018, 11:26 a.m.
Contrary to HAE types 1 and 2, HAE type 3 occurs mainly in women and attacks are often associated with increased estrogen levels (pregnancy, oral contraception, hormonal replacement therapy).Created: 3 Jul 2018, 11:24 a.m.
Comment on mode of pathogenicity: added Mode of Pathogenicity as suggested by external expert reviewCreated: 3 Jul 2018, 10:47 a.m.
Comment on publications: added publications suggested from external expert review to support upgrading of the gene to GreenCreated: 3 Jul 2018, 10:46 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 supplied by GRID. GRID Gene Symbol HGNC PanelApp check: F12, GRID_Gene_Symbol: F12, GRID_Transcript_ENS_Community submitted: ENST00000253496, GRID_Transcript_RefSeq: NM_000505.3, GRID_Transcript_ENS_used_on_Production: ENST00000253496Created: 17 Apr 2018, 12:12 p.m.
Phenotypes for gene: F12 were changed from Angioedema, Hereditary, Type III; hereditary angioedema to Angioedema, hereditary, 3, OMIM:610618
Source NHS GMS was added to F12.
Source North West GLH was added to F12.
Source London North GLH was added to F12.
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.
Gene: f12 has been classified as Green List (High Evidence).
Gene: f12 has been classified as Green List (High Evidence).
Publications for gene: F12 were set to 16638441; 17186468; 19178938
Phenotypes for gene: F12 were set to Angioedema, Hereditary, Type III; hereditary angioedema
Mode of inheritance for gene: F12 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity for gene: F12 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: F12 were set to 16638441; 17186468
Victorian Clinical Genetics Services was added to F12. Panel: Primary immunodeficiency disorders
Expert Review Amber was added to F12. Panel: Primary immunodeficiency disorders
Phenotypes for gene F12 were set to Angioedema, Hereditary, Type III
F12 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
F12 was created by Louise Daugherty