Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672606 | SCV000797724 | likely pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2018-02-13 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000672606 | SCV001339265 | likely pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2020-03-24 | criteria provided, single submitter | clinical testing | Variant summary: RMRP n.-12_-4dupAGCTGAGGA is located in the untranslated mRNA region upstream of the initiation codon. This variant involves the duplication of 9 nucleotides in the promoter region of the RMRP gene, which is located between the TATA box (-33 to -25) and the transcription initiation site. Other duplications and insertions in this promoter region have been classified as pathogenic (internally and in ClinVar). The variant was absent in 127922 control chromosomes (gnomAD). These data do not allow any conclusion about variant significance. To our knowledge, no occurrence of n.-12_-4dupAGCTGAGGA in individuals affected with Cartilage-Hair Hypoplasia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV001215335 | SCV001387073 | pathogenic | Anauxetic dysplasia | 2023-05-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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). ClinVar contains an entry for this variant (Variation ID: 556583). 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 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 present in population databases (no rsID available, gnomAD 0.002%). This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. |
| Fulgent Genetics, |
RCV002493113 | SCV002793959 | likely pathogenic | Anauxetic dysplasia 1; Metaphyseal chondrodysplasia, McKusick type; Metaphyseal dysplasia without hypotrichosis | 2022-04-21 | criteria provided, single submitter | clinical testing |