Inherited bleeding disorders

Gene: F12

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.

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: 21 Mar 2022, 2:32 p.m.

Panel Version: 1.164

Comment on list classification: Changed rating from Grey to Green based on expert list/supporting information from the NIHRBR-RD BRIDGE project

Created: 9 Aug 2017, 1:23 p.m.

Green List (high evidence)

Current level of evidence and expert review, High level of confidence as disease-causing gene. Proven in 3 unrelated pedigrees via cosegregation analysis or less than 3 or 1 large pedigree supported with functional studies (animal model). Ready for clinical reporting. Previous comments from expert reviewer, observed in the NIHRBR-RD BRIDGE cohort.

Created: 9 Aug 2017, 12:32 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Coagulaton disorder; Angioedema, hereditary, type 3; Factor 12 deficiency

Publications

• 2882793

Variants in this GENE are reported as part of current diagnostic practice