Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000672299 | SCV000797395 | likely pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2018-01-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001209862 | SCV001381315 | likely pathogenic | Anauxetic dysplasia | 2019-05-29 | criteria provided, single submitter | clinical testing | This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. While this variant is present in population databases (rs727502777), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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 similar insertions and duplications immediately upstream of the coding sequence have been reported in individuals affected with cartilage-hair hypoplasia (PMID: 11207361, 16244706). ClinVar contains an entry for this variant (Variation ID: 556306). 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. |