ClinVar Miner

Submissions for variant NR_003051.3(RMRP):n.-24_-10dup (rs727502776)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000015279 SCV000789535 likely pathogenic Metaphyseal chondrodysplasia, McKusick type 2017-02-09 criteria provided, single submitter clinical testing
Invitae RCV000694726 SCV000823184 likely pathogenic Anauxetic dysplasia 2018-12-27 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. This variant duplicates a span of 15 nucleotides of the promoter region and three nucleotides of the open reading frame of the RMRP gene. 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 been reported in several individuals affected with cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders (PMID: 17015150, 25616543). This variant is also known as g.-25-11 dupACTACTCTGTGAAGC in the literature  (PMID: 17015150, 25616543). ClinVar contains an entry for this variant (Variation ID: 14211). This variant is located in the promoter region between the TATA box and the transcription initiation site. Experimental analyses using patient-derived cells from patients with RMRP promoter variants, as well as in vitro transfection studies, have shown that these promoter insertions result in silencing of RMRP transcription and reduced expression of the gene product (PMID: 11207361, 16254002). 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.
OMIM RCV000015279 SCV000035538 pathogenic Metaphyseal chondrodysplasia, McKusick type 2001-01-26 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.