Submissions for variant NR_003051.3(RMRP):n.-25_-13dup

dbSNP: rs1554651508

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000549540	SCV000640114	pathogenic	Anauxetic dysplasia	2023-10-28	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 not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of cartilage-hair hypoplasia (PMID: 21396580, 24217815; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 g.-26_-14dup. ClinVar contains an entry for this variant (Variation ID: 465207). 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.
Natera, Inc.	RCV001834783	SCV002075602	likely pathogenic	Metaphyseal chondrodysplasia, McKusick type	2021-02-01	no assertion criteria provided	clinical testing