Cytopenia - NOT Fanconi anaemia
Gene: RPL9The rating of this gene has been updated following NHS Genomic Medicine Service approval. It has been agreed that RPL9 should be amber.Created: 4 Mar 2022, 9:49 a.m. | Last Modified: 4 Mar 2022, 9:54 a.m.
Panel Version: 1.57
Comment on list classification: Current Green rating is based on consensus from GLHs, so will remain Green. Excluding the VUS, only two unrelated cases published with the same variant, but including functional data. The 'for-review' tag has been added in view of this evidence and recent Red review by Zornitza Stark on a Green gene.Created: 30 Sep 2020, 3:30 p.m. | Last Modified: 20 Oct 2020, 11:25 a.m.
Panel Version: 1.30
Not associated with any phenotype in OMIM or G2P
- PMID: 20116044 (2010) - Heterozygous missense variant (c.375G>C, p.Arg125Ser) in RPL9 identified in one proband and his affected mother with Diamond-Blackfan Anemia, but this was declared a VUS since patient cells did not show a pre-rRNA processing defect similar to that observed upon knockdown of RPL9 with siRNAs.
- PMID: 29114930 (2018) - One male patient with Diamond-Blackfan anaemia reported with a de novo splice site variant (c.-2+1G>C) in RPL9. Additional features included colitis, hypertelorism, epicanthus, micrognathia, webbed neck, thumb abnormalities, bicuspid aortic valve. No functional studies were undertaken.
- PMID: 31799629 (2020) - Female infant diagnosed with Diamond-Blackfan anaemia carrying the de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Phenotypic overlap can be seen with the previously reported case with the same variant, including colitis, thumb anomaly, and microcephaly. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.Created: 30 Sep 2020, 3:23 p.m. | Last Modified: 30 Sep 2020, 3:23 p.m.
Panel Version: 1.25
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Diamond Blackfan anaemia
Publications
PMID: 29114930, de novo splice site variant, c.-2+1G>C, functional impact of this variant is likely deleterious but not proven. Inherited missense variant reported in PMID 20116044, p.Arg125Ser is present in 31 hets in gnomad. PMID 23718193, cannot find RPL9 variant in main results table.Created: 14 Sep 2020, 8:29 a.m. | Last Modified: 14 Sep 2020, 8:37 a.m.
Panel Version: 1.6
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Diamond Blackfan anaemia
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, 1:52 p.m. | Last Modified: 22 Jul 2019, 1:52 p.m.
Panel Version: 0.95
New review/rating by Frances Smith, Viapath Kings College Hospital (Curation_Template_GMS_Haem_FS_updated_reviews_20190425.xlsx) on behalf of London South GLH for the GMS Haematology specialist test group. Gene rated as Green.Created: 4 May 2019, 8:55 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: RPL9; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Phenotypes: Diamond-Blackfan anemia; PMID(s): 23718193;20116044Created: 6 Feb 2019, 3:13 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: 6 Feb 2019, 3:12 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: RPL9.
Source Expert Review Amber was added to RPL9. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Tag for-review tag was added to gene: RPL9.
Gene: rpl9 has been classified as Green List (High Evidence).
Gene: rpl9 has been classified as Green List (High Evidence).
Source London South GLH was added to RPL9.
Publications for gene: RPL9 were set to 23718193; 20116044
Source NHS GMS was added to RPL9.
Source Expert Review Green was added to RPL9. Mode of inheritance for gene RPL9 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Diamond-Blackfan anemia for gene: RPL9 Publications for gene RPL9 were changed from to 23718193; 20116044 Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: RPL9 was added gene: RPL9 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: RPL9 was set to