Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174592 | SCV001337783 | likely pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2020-01-16 | criteria provided, single submitter | clinical testing | Variant summary: The RMRP n.-3_1dupCGTG variant involves the duplication of 4 nucleotides in the promoter region/ trasncriptional start-site of RMRP. Many other insertions or duplications in the promoter region of RMRP have been reported as pathogenic or likely pathogenic (internally, in ClinVar, and in the literature). Several laboratories have reported functional studies suggesting that other mutations in the promoter region of RMRP silence transcription (e.g. Ridanpaa_2001, Hermanns_2005). The variant was absent in 128028 control chromosomes (gnomAD). n.-3_1dupCGTG has been reported in the literature (as n.-4_-1dup) in trans with another promoter region variant in one individual affected with combined immune deficiency (CID) and CD8 lymphopenia (Kavadas_2008). To our knowledge, no experimental evidence demonstrating an impact on RMRP function has been reported for this variant. 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 likely pathogenic. |
| Invitae | RCV001246209 | SCV001419550 | uncertain significance | Anauxetic dysplasia | 2021-07-14 | 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of cartilage hair hypoplasia (PMID: 18804272). This variant is also known as -4_-1 dup. ClinVar contains an entry for this variant (Variation ID: 917560). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant 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. |