Submissions for variant NM_005373.3(MPL):c.1468+2T>C

dbSNP: rs1057517761

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412964	SCV000490616	pathogenic	not provided	2015-03-11	criteria provided, single submitter	clinical testing	The c.1468+2 T>C splice sitevariant in the MPL gene destroys the canonical splice donor site in intron 9. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that issubject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. We interpret c.1468+2 T>C to be a pathogenic variant.
Invitae	RCV002524635	SCV003263139	likely pathogenic	Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia	2022-06-18	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 372410). This variant has not been reported in the literature in individuals affected with MPL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the MPL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MPL are known to be pathogenic (PMID: 8073287, 11133753).