Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000665120 | SCV000789186 | likely pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2017-01-20 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001240786 | SCV001413758 | pathogenic | Anauxetic dysplasia | 2024-01-27 | 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 0.02%). This variant has been observed in individual(s) with cartilage-hair hypoplasia (CHH) (PMID: 15780958, 16838329). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as -4_-23dup, -5_-24dup, and -6_-25dup. ClinVar contains an entry for this variant (Variation ID: 550387). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects RMRP function (PMID: 16254002). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000665120 | SCV001572342 | pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2021-04-05 | criteria provided, single submitter | clinical testing | Variant summary: RMRP n.-22_-3dup20 involves the duplication of 20 nucleotides in the promoter region of RMRP, which is located between the TATA box (-33 to -25) and the transcription initiation site. Other insertions or duplications in the promoter region of RMRP have been classified as pathogenic (internally and in ClinVar). The variant allele was found at a frequency of 5.7e-05 in 158744 control chromosomes (all heterozygotes). The variant has been reported in the literature in multiple individuals affected with Cartilage-Hair Hypoplasia (Harada_2005, Hermanns_2006, Turkkani-Asal_2009). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, and demonstrated that the variant resulted in severely reduced RMRP transcription (Hermanns_2005). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic (n=1) / likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
Fulgent Genetics, |
RCV002493080 | SCV002777835 | pathogenic | Anauxetic dysplasia 1; Metaphyseal chondrodysplasia, McKusick type; Metaphyseal dysplasia without hypotrichosis | 2022-05-05 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000665120 | SCV002075570 | pathogenic | Metaphyseal chondrodysplasia, McKusick type | 2020-09-29 | no assertion criteria provided | clinical testing |