Bleeding and platelet disorders
Gene: F12
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Green, and the mode of inheritance of this gene has not been changed and remains 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
GMS reviewers note that defects in F12 are associated with prolonged APTT; therefore, this should remain a green gene in the R90 panel. It should be left on the panel as may explain prolonged aPTT if not bleeding, so potentially still useful in the diagnostic pathway. As with most genes encoding coagulation factors, both monoallelic and biallelic F7 variants can be clinically significant.Created: 1 Feb 2023, 7:59 a.m. | Last Modified: 1 Feb 2023, 8:08 a.m.
Panel Version: 2.3
Added the Q2_22_rating tag to make it clear that both the rating and the MOI of this gene is being considered.Created: 6 Oct 2022, 2:36 p.m. | Last Modified: 6 Oct 2022, 2:36 p.m.
Panel Version: 1.44
This gene will be flagged for GMS review regarding the pertinence of monoallelic variants to this panel and whether the MOI should remain as 'both mono- and biallelic' or changed to 'biallelic' only or whether this gene should be demoted on this panel altogether.
Monoallelic variants are associated with hereditary angioedema (MIM# 610618) characterised clinically by recurrent skin swelling, abdominal pain attacks, and episodes of upper airway obstruction but otherwise patients do not display any strong evidence of abnormal bleeding or clotting phenotypes. Biallelic variants cause a separate disorder, factor XII deficiency (MIM# 234000) associated with hypercoagulation which in some cases has been linked to thrombus formation.Created: 21 Mar 2022, 2:32 p.m. | Last Modified: 4 Apr 2022, 9:28 a.m.
Panel Version: 1.36
No abnormal bleeding, asymptomatic prolonged PTT.Created: 12 Aug 2020, 3:50 a.m. | Last Modified: 12 Aug 2020, 3:50 a.m.
Panel Version: 1.6
Phenotypes
Factor XII deficiency, MIM# 234000
Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test groupCreated: 18 Feb 2019, 11:23 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
234000 Factor XII deficiency, hereditary Angioedema type III
Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.Created: 13 Feb 2019, 11:32 a.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
234000 Factor XII deficiency, hereditary Angioedema type III
Gene rating submitted by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group.Created: 7 Feb 2019, 1:21 p.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
234000 Factor XII deficiency, hereditary Angioedema type III
Variants in this GENE are reported as part of current diagnostic practice
Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: F12; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 234000 Factor XII deficiency, hereditary Angioedema type III; PMID(s): none submittedCreated: 18 Feb 2019, 11:28 a.m.
Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: F12; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Phenotypes: 234000 Factor XII deficiency, hereditary Angioedema type III; PMID(s): none submittedCreated: 13 Feb 2019, 11:34 a.m.
Initial gene list (Consensus Genes for Panels_Bleeding and Thrombosis_South London.xlsx) collated by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: F12; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Phenotypes: 234000 Factor XII deficiency, hereditary Angioedema type III; PMID(s): none submittedCreated: 7 Feb 2019, 1:28 p.m.
Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: F12; Suggested intial gene rating: Green List (high evidence); Are variants in this gene as part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 234000 Factor XII deficiency; 610618 Hereditary Angioedema type III; PMID(s): 27003566; 9354665; 20386432Created: 5 Feb 2019, 1:26 p.m.
Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.Created: 5 Feb 2019, 11:19 a.m.
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_22_rating was removed from gene: F12. Tag Q2_22_MOI was removed from gene: F12. Tag Q2_22_phenotype was removed from gene: F12. Tag Q2_22_expert_review was removed from gene: F12.
Tag Q2_22_rating tag was added to gene: F12.
Phenotypes for gene: F12 were changed from 234000 Factor XII deficiency; 234000 Factor XII deficiency, hereditary Angioedema type III; 610618 Hereditary Angioedema type III to Angioedema, hereditary, type III, OMIM:610618; Factor XII deficiency, OMIM:234000
Tag Q2_22_MOI tag was added to gene: F12. Tag Q2_22_phenotype tag was added to gene: F12. Tag Q2_22_expert_review tag was added to gene: F12.
Added phenotypes 234000 Factor XII deficiency, hereditary Angioedema type III for gene: F12
Source North West GLH was added to F12.
Added phenotypes 234000 Factor XII deficiency, hereditary Angioedema type III for gene: F12
Source Yorkshire and North East GLH was added to F12.
Added phenotypes 234000 Factor XII deficiency, hereditary Angioedema type III for gene: F12
Source London South GLH was added to F12.
Source NHS GMS was added to F12.
Source Expert Review Green was added to F12. Mode of inheritance for gene F12 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes 234000 Factor XII deficiency; 610618 Hereditary Angioedema type III for gene: F12 Publications for gene F12 were changed from to 9354665; 20386432; 27003566 Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: F12 was added gene: F12 was added to Bleeding and platelet disorders. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: F12 was set to