Inherited bleeding disorders (Version 1.177)

Description

This panel also covers Monogenic venous thrombosis - please see https://www.genomicsengland.co.uk/information-for-gmc-staff/rare-disease-documents/ for details of the eligibility criteria.

Inherited bleeding and or platelet disorders inclusion criteria :

Diagnosis of a bleeding and/or platelet disorder* of unknown cause before the age of 50 and following haematological consultation, AND family history or consanguineous parents,
OR syndromic features (incl. neurodevelopmental, immunological, nephrology, skeletal, hearing, etc.),
OR early onset severe childhood case of unknown cause
OR deficiency of coagulation factor without causal coding variants in the corresponding gene.

*Platelet disorder is defined as one or more of the following:
Platelet count greater than 400x10e9/L or less than 100x10e9/L
Mean Platelet Volume (MPV) greater than 13 fL and /or macrothrombocytopenia, or MPV less than 7fL
Abnormal platelet morphology, ideally confirmed by high resolution microscopy
Abnormal platelet function test, replicated on an independent sample

Inherited bleeding and or platelet disorders exclusion criteria :

1. Acquired bleeding and /or platelet disorders

2. Cases with platelet counts greater than 400x10e9/L and age less than 30 must be tested and found to be negative for somatic mutations in JAK2 and CALR

3. Use of prescription or over-the-counter drugs known to be associated with abnormal platelet (function) phenotypes and/or bleeding disorders, including
a. anticoagulant medications
b. aspirin, clopidogrel, dipyridamole, etc.
c. nonsteroidal anti-inflammatory drugs (incl. COX-2 selective anti-inflammatory drugs)

4. Patients with evidence of an autoimmune or other systemic condition known to affect
haemostasis and platelet homeostasis, including
a. Autoimmune thrombocytopenia (ITP)
b. Other autoimmune disorders, e.g. SLE

5. Other medical conditions known to be associated with abnormal platelet count and volume and / or abnormal platelet function
a. Acute viral infection
b. Bone marrow aplasia
c. DIC (Disseminated intravascular coagulation)
d. Hepatic failure
e. HIV positivity and/or AIDS
f. HUS (Haemolytic-uraemic syndrome)
g. Malignancies, particularly those compromising haematopoiesis
h. Splenomegaly
i. TTP (Thrombotic thrombocytopenia purpura)
j. Uraemia

Prior genetic testing guidance :

- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Inherited bleeding and or platelet disorders prior genetic testing genes :
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
SERPINC1, PROC, PROS1, SERPIND1, HRG, PLG, THBD, PLAT

Closing statement :
These requirements will be kept under continual review during the main programme and may be subject to change.

This panel includes BRIDGE consortium Tier 1 genes sent by Karyn Megy, WGS Clinical Feedback Lead, NIHR BioResource – Rare Diseases Study (NIHRBR-RD) on 10th March 2016.

The following experts contributed to the Bleeding thrombotic and Platelet Disorders list:
Prof Willem Ouwehand, Director NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Prof Kathleen Freson, Centre for Molecular and Vascular Biology, Leuven, Belgium
Prof Michael Laffan, Imperial College, London
Dr Andrew Mumford, University of Bristol
Dr Keith Gomez, Royal Free Hospital, London
Dr Kate Downes, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Dr Ernest Turro, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Dr Ilenia Simeoni, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Dr Karyn Megy, , NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust

Panel Activity

8 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
BRIDGE consortium (NIHRBR-RD)

Group: Other
Workplace: Other
Neil Morgan (University of Birmingham)

Group: GeCIP domain
Workplace: Research lab
Kate Downes (Uni of Cambridge / CUH)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other

119 Entities

113 reviewed, 103 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 119 Entitiess
Green Green List (high evidence)	ABCG5	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Platelet disorder Sitosterolemia and Thrombocytopenia Tags
Green Green List (high evidence)	ABCG8	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Platelet disorder Sitosterolemia and Thrombocytopenia Tags
Green Green List (high evidence)	ACTB	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Baraitser-Winter syndrome 1 with macrothrombocytopenia Platelet disorder Tags
Green Green List (high evidence)	ACTN1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Macrothrombocytopenia Tags
Green Green List (high evidence)	ACVRL1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes Telangiectasia, hereditary hemorrhagic, type 2, 600376 Bleeding disorder Tags
Green Green List (high evidence)	ADAMTS13	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Research Phenotypes Thrombotic thrombocytopenic purpura, hereditary, OMIM:274150 Tags
Green Green List (high evidence)	ANKRD26	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Thrombocytopenia 2 Tags
Green Green List (high evidence)	ANO6	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Scott syndrome Tags
Green Green List (high evidence)	AP3B1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	AP3D1	2 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes ?Hermansky-Pudlak syndrome 10 Platelet disorder Hermansky-Pudlak syndrome and MR Tags
Green Green List (high evidence)	ARPC1B	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718 Combined immune deficiency with or without thrombocytopenia Inflammatory predisposition Tags
Green Green List (high evidence)	BLOC1S3	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	BLOC1S6	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	CDC42	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Literature Phenotypes Takenouchi-Kosaki syndrome, 616737 Platelet disorder Tags de novo
Green Green List (high evidence)	CHST14	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE consortium (NIHRBR-RD) Expert Review Green Phenotypes Ehlers-Danlos syndrome, musculocontractural type Tags
Green Green List (high evidence)	COL1A1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Bleeding disorder Ehlers-Danlos syndrome Caffey Osteogenesis imperfecta type 1 Osteogenesis imperfecta type 2 Osteogenesis imperfecta type 3 Osteogenesis imperfecta type 4 Tags
Green Green List (high evidence)	COL5A1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Bleeding disorder Ehlers-Danlos syndrome, classic type Tags
Green Green List (high evidence)	COL5A2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Bleeding disorder Ehlers-Danlos syndrome, classic type Tags
Green Green List (high evidence)	CYCS	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Thrombocytopenia 4, OMIM:612004 Tags
Green Green List (high evidence)	DIAPH1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Macrothrombocytopenia and sensorineural hearing loss Tags
Green Green List (high evidence)	DTNBP1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	ENG	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes Telangiectasia, hereditary hemorrhagic, type 1, 187300 Bleeding disorder Tags
Green Green List (high evidence)	ETV6	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukaemia Tags
Green Green List (high evidence)	F10	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Factor X deficiency Tags
Green Green List (high evidence)	F11	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Factor XI deficiency Tags
Green Green List (high evidence)	F12	3 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Angioedema, hereditary, type III, OMIM:610618 Factor XII deficiency, OMIM:234000 Tags watchlist_moi
Green Green List (high evidence)	F13A1	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Factor XIIIA deficiency, OMIM:613225 Tags
Green Green List (high evidence)	F13B	3 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Phenotypes Factor XIIIB deficiency, OMIM:613235 Tags
Green Green List (high evidence)	F2	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Prothrombin deficiency Thrombophilia Due To Thrombin Defect Dysprothrombinemia 613679 Hypoprothrombinemia 613679 Thrombophilia due to thrombin defect 188050 Prothrombin-Related Thrombophilia Tags
Green Green List (high evidence)	F5	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Factor V deficiency Thrombophilia, susceptibility to, due to factor V Leiden 188055 Thrombophilia due to activated protein C resistance 188055 Factor V Cambridge Thrombophilia Factor V Leiden Thrombophilia Factor V R2 Mutation Thrombophilia Thrombophilia Due To Activated Protein C Resistance Tags
Green Green List (high evidence)	F7	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Factor VII deficiency Tags
Green Green List (high evidence)	F8	4 reviews 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Haemophilia A Tags gene-therapy-trial non-coding-known-pathogenic
Green Green List (high evidence)	F9	3 reviews 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Haemophilia B Thrombophilia, X-linked, due to factor IX defect 300807 Tags gene-therapy-trial
Green Green List (high evidence)	FERMT3	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Leukocyte integrin adhesion deficiency, type III Tags
Green Green List (high evidence)	FGA	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Fibrinogen deficiency Hypodysfibrinogenemia,congenital,616004 Dysfibrinogenemia,congenital,616004 thrombosis Fibrinogen Dusart dysfibrinogenemia associated with recurrent thrombosis thrombophilia prolonged thrombin clotting Fibrinogen Caracas II Tags
Green Green List (high evidence)	FGB	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Fibrinogen deficiency Dysfibrinogenemia,congenital,616004 dysbetafibrinogenemia with thrombosis Thrombophilia in association with congenital dysfibrinogenemia Tags
Green Green List (high evidence)	FGG	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Fibrinogen deficiency Dysfibrinogenemia,congenital,616004 Dysfibrinogenemia, congenita Hypodysfibrinogenemia Tags
Green Green List (high evidence)	FLI1	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Paris-Trousseau thrombocytopenia and Jacobson syndrome (BIALLELIC, autosomal or pseudoautosomal) Bleeding disorder, platelet-type, 21 617443 BDPLT21 BDPLT21, Storage Pool Disorder and Bleeding (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown) BDPLT21, Paris Trousseau like (BIALLELIC, autosomal or pseudoautosomal) Bleeding disorder, platelet-type, 21 Tags
Green Green List (high evidence)	FLNA	3 reviews 1 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Heterotopia, periventricular, 1, OMIM:300049 Macrothrombocytopenia Tags
Green Green List (high evidence)	FYB1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Thrombocytopenia 3, 273900 Platelet disorder Microthrombocytopenia 3 Tags
Green Green List (high evidence)	GATA1	2 reviews 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes X-linked thrombocytopenia with dyserythropoiesis Tags
Green Green List (high evidence)	GBA	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Gaucher disease Gaucher disease, perinatal lethal, 608013 Gaucher disease, type I, 230800 Gaucher disease, type II,230800 Gaucher disease, type III, 230800 Gaucher disease, type IIIC, 231005 Tags new-gene-name
Green Green List (high evidence)	GFI1B	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Gray platelet-like syndrome (GPS) Bleeding disorder, platelet-type, 17 (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown) 187900 Combined alpha-delta platelet storage pool deficiency (BIALLELIC, autosomal or pseudoautosomal) Tags
Green Green List (high evidence)	GGCX	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Multiple coagulation factor deficiency type 3 Tags
Green Green List (high evidence)	GNE	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Myopathy associated with thrombocytopenia Tags
Green Green List (high evidence)	GP1BA	3 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Phenotypes Bernard-Soulier syndrome, type A1 (recessive) 231200 Platelet-type von Willebrand disease Bernard-Soulier syndrome Bernard-Soulier syndrome (BIALLELIC, autosomal or pseudoautosomal) Platelet-type von Willebrand disease (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown) Tags
Green Green List (high evidence)	GP1BB	3 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Phenotypes Bernard-Soulier syndrome, type B, OMIM:231200 Giant platelet disorder, isolated, OMIM:231200 Macrothrombocytopenia Tags
Green Green List (high evidence)	GP6	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Bleeding disorder, platelet-type, 11, OMIM:614201 Tags
Green Green List (high evidence)	GP9	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Other Phenotypes Bernard-Soulier syndrome, type C 231200 Bernard-Soulier syndrome Tags
Green Green List (high evidence)	HOXA11	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Amegakaryocytic thrombocytopenia with radioulnar synostosis Tags
Green Green List (high evidence)	HPS1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	HPS3	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	HPS4	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	HPS5	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	HPS6	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Hermansky-Pudlak syndrome Tags
Green Green List (high evidence)	HRG	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Histidine-rich glycoprotein deficiency Thrombophiliadue to elevated HRG Thrombophilia due to HRG deficiency Thrombophilia due to elevated HRG 613116 Thrombophilia due to HRG deficiency 613116 Tags missense
Green Green List (high evidence)	IKZF5	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Thrombocytopenia Tags
Green Green List (high evidence)	ITGA2B	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Glanzmann thrombasthenia (BIALLELIC, autosomal or pseudoautosomal) 273800 Bleeding disorder, platelet-type, 16, autosomal dominant (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown ) 187800 BDPLT16 Congenital macrothrombocytopenia Tags
Green Green List (high evidence)	ITGB3	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Glanzmann thrombasthenia (BIALLELIC, autosomal or pseudoautosomal) 273800 Bleeding disorder, platelet-type, 16, autosomal dominant (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown) 187800 BDPLT16 Congenital macrothrombocytopenia Tags
Green Green List (high evidence)	KDSR	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Platelet disorder Severe Thrombocytopenia with progression to marrow fibrosis at young age Tags
Green Green List (high evidence)	KLKB1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Fletcher factor (prekallikrein) deficiency, 612423 Fletcher syndrome Coagulation disorder Tags
Green Green List (high evidence)	KNG1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Coagulaton disorder High Molecular Weight Kininogen Deficiency Tags
Green Green List (high evidence)	LMAN1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Combined factor V and VIII deficiency Tags
Green Green List (high evidence)	LYST	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Chediak-Higashi syndrome (CHS) Tags
Green Green List (high evidence)	MCFD2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Combined factor V and VIII deficiency Tags
Green Green List (high evidence)	MECOM	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738 Tags
Green Green List (high evidence)	MPIG6B	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Phenotypes Platelet disorder Thrombocytopenia, anemia, and myelofibrosis Tags
Green Green List (high evidence)	MPL	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Thrombocytopenia, congenital amegakaryocytic, OMIM:604498 Tags
Green Green List (high evidence)	MYH9	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes May-Hegglin and other MYH9 disorders Tags
Green Green List (high evidence)	NBEA	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Dense granule abnormality Tags
Green Green List (high evidence)	NBEAL2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Gray platelet syndrome Tags
Green Green List (high evidence)	P2RY12	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes ADP receptor defect Tags
Green Green List (high evidence)	PLA2G4A	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Deficiency of phospholipase A2, group IV A Tags
Green Green List (high evidence)	PLAT	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Other Phenotypes Tissue Plasminogen Activator deficiency Thrombophilia, familial, due to decreased release of PLAT 612348 Thrombophilia due to decreased release of tissue plasminogen Tags
Green Green List (high evidence)	PLAU	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Quebec platelet disorder Tags
Green Green List (high evidence)	PLG	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Phenotypes Plasminogen deficiency, type I, OMIM:217090 Dysplasminogenemia, OMIM:217090 Tags
Green Green List (high evidence)	PROC	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Protein C deficiency Protein C Deficiency Thrombophilia due to protein C deficiency, autosomal dominant 176860 Thrombophilia due to protein C deficiency, autosomal recessive 612304 Thrombophilia Due To Protein C Deficiency, Autosomal Dominant Thrombophilia Due To Protein C Deficiency, Autosomal Recessive Tags
Green Green List (high evidence)	PROS1	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Protein S deficiency Thrombophilia Due To Protein S Deficiency, Autosomal Dominant Thrombophilia Due To Protein S Deficiency, Autosomal Recessive Thrombophilia due to protein S deficiency, autosomal dominant 612336 Thrombophilia due to protein S deficiency, autosomal recessive 614514 Protein S Deficiency Tags
Green Green List (high evidence)	PTPN11	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Bleeding disorder LEOPARD syndrome, Leukemia, Juvenile myelomonocytic, somatic Metachondromatosis Noonan syndrome Tags
Green Green List (high evidence)	RASGRP2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Platelet-type bleeding disorder 18 Tags
Green Green List (high evidence)	RBM8A	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Thrombocytopenia-absent radius syndrome (TAR) Tags
Green Green List (high evidence)	RNU4ATAC	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Platelet disorder Roifman Syndrome with thrombocytopenia and Primary immunodeficiency Tags locus-type-rna-small-nuclear
Green Green List (high evidence)	RUNX1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Familial platelet disorder with predisposition to acute myelogenous leukemia Tags
Green Green List (high evidence)	SERPINC1	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Thrombophilia due to antithrombin III deficiency, OMIM:613118 Tags
Green Green List (high evidence)	SERPIND1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Heparin cofactor 2 deficiency Thrombophilia due to heparin cofactor II deficiency,612356 Thrombophilia due to heparin cofactor II deficiency 612356 Tags
Green Green List (high evidence)	SERPINE1	3 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Illumina TruGenome Clinical Sequencing Services Other Radboud University Medical Center, Nijmegen Phenotypes Plasminogen activator Inhibitor 1 deficiency Plasminogen Activator Inhibitor-1 Deficiency Thrombophilia due to increased concentration of plasminogen activator inhibitor thrombophilia associated with high levels of plasminogen activator inhibitor Plasminogen activator inhibitor-1 deficiency,613329 Transcription of plasminogen activator inhibitor, modulator of Tags
Green Green List (high evidence)	SERPINF2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Alpha 2 antiplasmin deficiency Tags
Green Green List (high evidence)	SLC45A2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Oculocutaneous albinism and in some cases with mild bleeding symptoms and platelet dense granule secretion defect Tags
Green Green List (high evidence)	SLFN14	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE consortium (NIHRBR-RD) Expert Review Green Phenotypes SLFN14-related thrombocytopenia Platelet disorder Bleeding Disorder, platelet-type, 20 Tags
Green Green List (high evidence)	SMAD4	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050 Bleeding disorder Tags
Green Green List (high evidence)	SRC	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Other Phenotypes Thrombocytopenia, Bleeding and myelofibrosis ?Thrombocytopenia 6,616937 Platelet disorder Tags
Green Green List (high evidence)	STIM1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Stormorken syndrome 185070 Tags missense
Green Green List (high evidence)	STXBP2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Familial hemophagocytic lymphohistiocytosis type 5 Tags
Green Green List (high evidence)	TBXA2R	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes {Bleeding disorder, platelet-type, 13, susceptibility to}, OMIM:614009 Tags
Green Green List (high evidence)	TBXAS1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Ghosal hematodiaphyseal syndrome, OMIM:231095 ?Thromboxane synthase deficiency, OMIM:614158 Bleeding disorder, platelet-type, 14, OMIM:614158 Tags
Green Green List (high evidence)	THBD	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources BRIDGE Study Tier 1 Gene Eligibility statement prior genetic testing Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Thrombomodulin deficiency Thrombophilia Due To Thrombomodulin Defect Thrombophilia due to thrombomodulin defect 614486 Tags
Green Green List (high evidence)	THPO	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Thrombocytopenia and thrombocythemia 1 Tags
Green Green List (high evidence)	TUBB1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE consortium (NIHRBR-RD) Expert Review Green Phenotypes Macrothrombocytopenia, Beta-tubulin 1 related Tags
Green Green List (high evidence)	VIPAS39	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes ARC syndrome (Arthrogryposis, renal dysfunction, and cholestasis 1) Tags
Green Green List (high evidence)	VKORC1	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Vitamin K-dependent clotting factors, combined deficiency of, 2, OMIM:607473 Tags
Green Green List (high evidence)	VPS33B	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes ARC syndrome (Arthrogryposis, renal dysfunction, and cholestasis 2) Tags
Green Green List (high evidence)	VWF	2 reviews 1 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes von Willebrand factordisorders von Willebrand factor type 1 von Willebrand factor type 2A von Willebrand factor type 2B von Willebrand factor type 2M von Willebrand factor type 2N von Willebrand factor type 3 Tags
Green Green List (high evidence)	WAS	2 reviews 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources BRIDGE Study Tier 1 Gene Expert Review Green Phenotypes Wiskott-Aldrich syndrome Tags gene-therapy-trial
Amber Amber List (moderate evidence)	LAT	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Other Phenotypes Immunodeficiency 52, 617514 Tags watchlist
Amber Amber List (moderate evidence)	ORAI1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Amber Phenotypes Stormorken syndrome Tags
Amber Amber List (moderate evidence)	PTPRJ	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Thrombocytopenia spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin. Tags watchlist
Amber Amber List (moderate evidence)	SLC35A1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Congenital disorder of glycosylation, type IIf, 603585 severe thrombocytopenia hemorrhages macrothrombocytopenia Tags watchlist
Amber Amber List (moderate evidence)	TPM4	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources BRIDGE Study Tier 1 Gene Expert Review Amber Phenotypes Platelet disorder Macrothrombocytopenia Tags
Red Red List (low evidence)	APOH	1 review	Not set	Sources Other Phenotypes risk of thrombosis antiphospholipid syndrome Tags
Red Red List (low evidence)	COL2A1	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Other Phenotypes Avascular necrosis of the femoral head feature of hereditary thrombophilia Legg-Calve-Perthes disease Tags
Red Red List (low evidence)	HABP2	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Illumina TruGenome Clinical Sequencing Services Phenotypes Venous thromboembolism, susceptibility to 188050 Factor VII Marburg I Variant Thrombophilia Tags
Red Red List (low evidence)	IFNAR2	0 reviews	Unknown	Sources Other Tags
Red Red List (low evidence)	LPA	1 review	Not set	Sources Other Phenotypes thromboembolism elevated serum Lp(a) levels childhood thrombosis associated with raised Lp(a) levels Tags
Red Red List (low evidence)	MTHFR	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Radboud University Medical Center, Nijmegen Phenotypes Thromboembolism, susceptibility to 188050 Tags
Red Red List (low evidence)	PIGA	1 review	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert list Expert Review Red Phenotypes Paroxysmal nocturnal haemoglobinuria, somatic, 300818 Tags Skewed X-inactivation somatic treatable
Red Red List (low evidence)	PROCR	0 reviews	Not set	Sources Other Phenotypes thrombosis Tags
Red Red List (low evidence)	PROZ	1 review	Not set	Sources Other Phenotypes Protein Z deficiency thromboembolic complication during pregnancy Tags
Red Red List (low evidence)	SERPINA10	0 reviews	Not set	Sources Other Phenotypes ZPI deficiency thrombophilia Tags
Red Red List (low evidence)	TFPI	1 review	Not set	Sources Other Phenotypes ?thrombophilia Tags

Inherited bleeding disorders (Version 1.177)

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