ClinVar Miner

Submissions for variant NR_003051.3(RMRP):n.-21_-19dup (rs1029136594)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665830 SCV000790011 uncertain significance Metaphyseal chondrodysplasia, McKusick type 2017-03-01 criteria provided, single submitter clinical testing
Invitae RCV000818342 SCV000958950 uncertain significance Anauxetic dysplasia 2018-08-10 criteria provided, single submitter clinical testing This sequence change occurs in the RMRP gene, which encodes the RNA component of the RNase mitochondrial RNA processing (MRP) complex and does not result in a protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with RMRP-related disease. While this particular variant has not been reported in the literature, it is located in the promoter region between the TATA box and the transcription initiation site, and other insertions and duplications in this region have been reported in individuals affected with cartilage-hair hypoplasia (PMID: 21063072, 23643676). In addition, experimental analyses using patient derived cells, as well as in vitro transfection studies, have shown that promoter insertions result in silencing of RMRP transcription and reduced expression of the gene product (PMID: 11207361, 16254002). However, the size of the insertions and duplications observed and tested in these studies were significantly larger than this 3bp duplication (n.-21_-19dup) and therefore the clinical significance of this smaller duplication is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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