Haematological malignancies cancer susceptibility

Gene: RPS15

Red List (low evidence)

The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 11:21 a.m. | Last Modified: 30 Jan 2023, 11:21 a.m.

Panel Version: 3.3

This gene has been flagged for GMS expert review as published evidence linking germline variants to haematological malignancies is limited, which may warrant a rating downgrade from Green, subject to review.
RPS15 somatic variants are enriched within chronic lymphocytic leukemia, particularly in aggressive cases - however, the contribution of germline variants is not well-defined.

Created: 1 Sep 2022, 10:39 a.m. | Last Modified: 1 Sep 2022, 10:39 a.m.

Panel Version: 2.36

Single missense variant was identified in a patient with Diamond-Blackfan anemia (PMID: 19061985) but at the time of reporting this individual did not suffer from cancer. This association with DBA has since been propagated in literature but no further cases since the initial paper have been published.
A number of studies have been released linking RPS15 to chronic lymphocytic leukemia - BUT due to somatic rather than germline variants (PMID: 26466571; 26675346; 30181176). Functional studies show variants lead to altered ribosomal function regarding both protein synthesis and translational fidelity (PMID: 30181176; 34251413)

Created: 1 Sep 2022, 10:33 a.m. | Last Modified: 1 Sep 2022, 10:33 a.m.

Panel Version: 2.34

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Diamond-Blackfan anemia; Chronic lymphocytic leukemia

Publications

• 19061985
• 26466571
• 26675346
• 30181176
• 34251413

Gene listed in Table 2 (Genes Involved in Predisposition to Hematologic Malignancies) in PMID:28297620

Created: 9 May 2022, 9:47 a.m. | Last Modified: 9 May 2022, 9:47 a.m.

Panel Version: 2.30

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown