The RPS20 gene encodes a protein required during the late steps of 18S ribosomal RNA (rRNA) formation. RPS20 was first reported in relation to autosomal dominant dominate Lynch syndrome in 2014 (Nieminen et al., PMID: 24941021). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found Lynch syndrome (MONDO: 0005835) is the only one disease entity associated with this gene at the time of this curation. This curation is based on this disease entity only. This gene-disease association is supported by genetic evidence (4.5 Points). Three variants (frameshift, splicing, missense) that have been reported in three probands in the first report and two recent publications (PMIDs: 24941021, 32424863, 33193653) are included in this curation. Segregation evidence from PMID: 24941021 is also included to support this gene-disease relationship. In addition, in vitro experiments showed that the RPS20 mutation led to a defect in pre–ribosomal RNA maturation and may further disturb the stabilization of p53 (0.5 Point). In summary, there is limited evidence to support this gene-disease relationship of RPS20 and autosomal dominant Lynch Syndrome. This gene-disease pair was originally evaluated as limited by the Colon Cancer GCEP on 06/08/2017. This re-curation was approved by the ClinGen Hereditary Cancer GCEP on 3/22/2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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