ClinVar Miner

Submissions for variant NM_033022.3(RPS24):c.1A>G (p.Met1Val) (rs886039545)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255670 SCV000322342 pathogenic not provided 2016-07-24 criteria provided, single submitter clinical testing The c.1 A>G pathogenic variant in the RPS24 gene has been reported previously in association with Diamond-Blackfan anemia (Badhai et al., 2009; Ghemlas et al., 2015). The c.1 A>G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. As this variant changes the translation initiator Methionine codon, the resultant protein is described as p.Met1?, using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. We interpret c.1 A>G as a pathogenic variant.
Invitae RCV000551919 SCV000637228 pathogenic Diamond-Blackfan anemia 2018-01-23 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the RPS24 mRNA. The next in-frame methionine is located at codon 13. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Diamond-Blackfan anemia (PMID: 19689926). In addition, it has been observed to be de novo in an individual with clinical features of Diamond-Blackfan anemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 265439). Experimental studies using patient derived fibroblasts have shown that this variant leads to decreased RPS24 and RPS19 protein levels, abnormal expression of cell cycle regulatory proteins, and reduced cellular proliferation (PMID: 19689926). For these reasons, this variant has been classified as Pathogenic.

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