Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781819 | SCV000920158 | pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2018-12-07 | criteria provided, single submitter | clinical testing | Variant summary: RMRP n.-13_1dup14 variant involves the duplication of 8 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 (internally and in HGMD). The variant allele was found at a frequency of 8.1e-06 in 123146 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in RMRP causing Cartilage-Hair Hypoplasia (8.1e-06 vs 0.0072), allowing no conclusion about variant significance. The variant, n.-13_1dup14, has been reported in the literature in one individual affected with Cartilage-Hair Hypoplasia, together with the founder mutation c.70A>G (Ridanpaa_2002). To our knowledge, no experimental evidence demonstrating an impact on protein function 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. |
| Labcorp Genetics |
RCV001297863 | SCV001486901 | pathogenic | Anauxetic dysplasia | 2024-01-02 | 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. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has been observed in individuals with cartilage-hair hypoplasia anauxetic dysplasia (CHH-AD) spectrum disorders (PMID: 12107819). Other insertions and duplications immediately upstream of the coding sequence have been reported in individuals affected with cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders (PMID: 16244706, 11207361, 12107819). This variant is also known as dup AAGCTGAGGACGTG at 1. 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). For these reasons, this variant has been classified as Pathogenic. |