ClinVar Miner

Submissions for variant NR_003051.3(RMRP):n.-24_-18dup (rs1554651543)

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 RCV000669457 SCV000794211 likely pathogenic Metaphyseal chondrodysplasia, McKusick type 2017-09-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000669457 SCV000920152 pathogenic Metaphyseal chondrodysplasia, McKusick type 2018-03-22 criteria provided, single submitter clinical testing Variant summary: The RMRP n.-24_-18dupACTACTC variant involves the duplication of 7 nucleotides in the promoter region of RMRP, which is located between the TATA box (-33 to -25) and the transcription initiation site. Multiple duplication variants in this promoter region have been reported pathogenic. The variant was absent in 139490 control chromosomes. n.-24_-18dupACTACTC has been reported homozygously in the literature in one individual affected with Cartilage-Hair Hypoplasia. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function for this variant has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000796285 SCV000935791 likely pathogenic Anauxetic dysplasia 2018-07-29 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 been observed as homozygous in an individual with cartilage hair hypoplasia (CHH) (PMID: 21063072). This variant is also known as g.-19_-25dupACTACTC in the literature. While functional studies for this variant have not been reported, 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). 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.

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.