Hereditary Erythrocytosis
Gene: JAK2
There is limited evidence to support an association of JAK2 variants with hereditary/congenital erythrocytosis. Typically, variants are somatic/acquired; and to date, only one report has described a patient with germline compound het variants (p.E846D and p.R1063H) in JAK2, who exhibited polyclonal erythrocytosis and megakaryocytic atypia but normal platelet number (PMID:27389715).
Note that this condition is distinct from polycythemia vera (PV), which is most commonly associated with JAK2 gain-of-function somatic variants, particularly p.V617F, but also with reports of some familial clustering due to inheritance of the JAK2 46/1 predisposition haplotype. Unlike PV, hereditary erythrocytosis is not associated with the risk of clonal evolution and should present with isolated erythrocytosis, often present since birth.Created: 25 Sep 2020, 10:56 a.m. | Last Modified: 25 Sep 2020, 10:56 a.m.
Panel Version: 1.14
Mode of inheritance
Other
Phenotypes
Erythrocytosis, somatic, 133100
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
Comment on list classification: An amber rating has been given to JAK2, as only somatic variants in this gene have been reported to be associated with Erythrocytosis, somatic 133100.Created: 22 Sep 2020, 3:11 p.m. | Last Modified: 22 Sep 2020, 3:11 p.m.
Panel Version: 1.12
GMS Expert review Green
Sources: Expert review, NHS GMSCreated: 18 Aug 2020, 4:26 p.m. | Last Modified: 18 Aug 2020, 4:35 p.m.
Panel Version: 1.8
Mode of inheritance
Unknown
Phenotypes
Erythrocytosis, somatic 133100
Phenotypes for gene: JAK2 were changed from Erythrocytosis, somatic 133100 to Erythrocytosis, somatic, OMIM:133100
Tag for-review was removed from gene: JAK2.
Mode of pathogenicity for gene: JAK2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for gene: JAK2 was changed from Unknown to Other
Tag for-review tag was added to gene: JAK2.
Gene: jak2 has been classified as Amber List (Moderate Evidence).
Gene: jak2 has been classified as Green List (High Evidence).
gene: JAK2 was added gene: JAK2 was added to Hereditary Erythrocytosis. Sources: Expert list,NHS GMS somatic tags were added to gene: JAK2. Mode of inheritance for gene: JAK2 was set to Unknown Phenotypes for gene: JAK2 were set to Erythrocytosis, somatic 133100 Review for gene: JAK2 was set to GREEN