Cytopenia - NOT Fanconi anaemia

Gene: MPL

Green List (high evidence)

MPL (MPL proto-oncogene, thrombopoietin receptor)
EnsemblGeneIds (GRCh38): ENSG00000117400
EnsemblGeneIds (GRCh37): ENSG00000117400
OMIM: 159530, Gene2Phenotype
MPL is in 6 panels

6 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval. GMS reviewers also note that the monoallelic variants that were previously reported for this gene were associated with thrombocythaemia and not with thrombocytopenia.
Created: 1 Feb 2023, 8:15 a.m. | Last Modified: 1 Feb 2023, 8:19 a.m.
Panel Version: 2.3

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: The MOI on this panel should be reviewed at the next GMS panel update to determine the pertinent inheritance pattern (currently set to both AD/AR).

Biallelic variants cause thrombocytopenia (MIM# 604498) which in severe forms can present with pancytopenia, a phenotype that is within the scope of this panel. On the other hand, monoallelic variants are associated with thrombocythemia (MIM# 601977) which does not include features that may be relevant here. Therefore it may be appropriate to update the MOI to 'biallelic' only.
Created: 12 Apr 2022, 11:26 a.m. | Last Modified: 12 Apr 2022, 11:26 a.m.
Panel Version: 1.63

Steve Keeney (Central Manchester Foundation Trust)

Green List (high evidence)

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 group.
Created: 18 Feb 2019, 2:55 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Thrombocytopenia, congenital amegakaryocytic, 604498

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

Mandy nesbitt (Healthcare Professional)

Green List (high evidence)

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: 14 Feb 2019, 5:39 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
604498 Thrombocytopenia, congenital amegakaryocytic

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

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Congenital amegakaryocytic thrombocytopenia (CAMT) presents with isolated thrombocytopenia in infancy and developing into a pancytopenia in later childhood); North West GLH: no comment submitted; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.
Created: 4 Nov 2019, 7:30 p.m. | Last Modified: 4 Nov 2019, 7:30 p.m.
Panel Version: 0.135
Comment on list classification: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.
Created: 22 Jul 2019, 1:24 p.m. | Last Modified: 22 Jul 2019, 1:24 p.m.
Panel Version: 0.79
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: MPL; Suggested initial 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, autosomal or pseudoautosomal; Phenotypes: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): 10077649; 18024606
Created: 18 Feb 2019, 2:57 p.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: MPL; Suggested initial 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, autosomal or pseudoautosomal; Phenotypes: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): none submitted
Created: 14 Feb 2019, 5:40 p.m.
Initial gene list (Consensus Genes for Haem Panels 17.12.18_KCH.xlsx) collated by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: MPL; 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, autosomal or pseudoautosomal; Phenotypes: 601977 Thrombocythemia 2; 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): 10077649; 11133753
Created: 8 Feb 2019, 1:43 p.m.

Frances Smith (King's College Hospital)

Green List (high evidence)

Gene rating submitted by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group.
Created: 8 Feb 2019, 1:36 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
601977 Thrombocythemia 2; 604498 Thrombocytopenia, congenital amegakaryocytic

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert review Green
  • Wessex and West Midlands GLH
  • Expert Review Green
  • North West GLH
  • Yorkshire and North East GLH
  • NHS GMS
  • London South GLH
Phenotypes
  • Thrombocytopenia, congenital amegakaryocytic, OMIM:604498
OMIM
159530
Clinvar variants
Variants in MPL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Feb 2023, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_22_MOI was removed from gene: MPL. Tag Q2_22_expert_review was removed from gene: MPL.

1 Feb 2023, Gel status: 3

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene MPL was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

12 Apr 2022, Gel status: 3

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: MPL was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

12 Apr 2022, Gel status: 3

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_22_MOI tag was added to gene: MPL. Tag Q2_22_expert_review tag was added to gene: MPL.

12 Apr 2022, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: MPL were changed from 601977 Thrombocythemia 2; 604498 Thrombocytopenia, congenital amegakaryocytic; Thrombocytopenia, congenital amegakaryocytic, 604498 to Thrombocytopenia, congenital amegakaryocytic, OMIM:604498

4 Nov 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Expert review Green was added to MPL.

4 Nov 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to MPL.

22 Jul 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: mpl has been classified as Green List (High Evidence).

18 Feb 2019, Gel status: 4

Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Added phenotypes Thrombocytopenia, congenital amegakaryocytic, 604498 for gene: MPL Publications for gene MPL were changed from 11133753; 10077649 to 10077649; 18024606

18 Feb 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to MPL.

14 Feb 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes 604498 Thrombocytopenia, congenital amegakaryocytic for gene: MPL

14 Feb 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to MPL.

8 Feb 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to MPL. Rating Changed from Red List (low evidence) to Green List (high evidence)

8 Feb 2019, Gel status: 1

Set mode of inheritance, Set Phenotypes

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene MPL was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes 601977 Thrombocythemia 2; 604498 Thrombocytopenia, congenital amegakaryocytic for gene: MPL

8 Feb 2019, Gel status: 1

Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Added phenotypes 601977 Thrombocythemia 2; 604498 Thrombocytopenia, congenital amegakaryocytic for gene: MPL Publications for gene MPL were changed from to 11133753; 10077649

8 Feb 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to MPL.

8 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: MPL was added gene: MPL was added to Cytopenia - NOT Fanconi anaemia. Sources: London South GLH Mode of inheritance for gene: MPL was set to