ClinVar Miner

Submissions for variant NR_003051.4(RMRP):n.182G>A

dbSNP: rs1004469515
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193442 SCV001362268 pathogenic Metaphyseal chondrodysplasia, McKusick type 2022-10-24 criteria provided, single submitter clinical testing Variant summary: RMRP n.181G>A alters a nucleotide in the non-coding RNA and was at the nucleotides involved in base pairing in the secondary structure of the RNA molecule, compromising the hairpin structure topology (Gomes_2019). Also, this variant was located in P12 domain which is important region for binding POP1 and RPP38 to the RNA molecule (PMID: 15096576). The variant allele was found at a frequency of 4.6e-05 in 130180 control chromosomes (gnomAD). n.181G>A has been reported in the literature in individuals affected with Cartilage-Hair Hypoplasia (Ridanpaa 2002, Hermanns 2005, Hermanns 2006, Castilla-Cortazar 2017, Gomes_2019). These data indicate that the variant is very likely to be associated with disease. At least one publication reported experimental evidence evaluating an impact on RMRP expression. The most pronounced variant effect results in 10%-<30% of normal RMRP expression (Hermanns 2005). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001390935 SCV001592837 pathogenic Anauxetic dysplasia 2023-12-10 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 0.03%). This variant has been observed in individual(s) with clinical features of cartilage-hair hypoplasia anauxetic dysplasia spectrum disorders (PMID: 16254002, 16838329, 27862957). This variant is also known as 180G>A and c.-542C>C/T. ClinVar contains an entry for this variant (Variation ID: 928881). For these reasons, this variant has been classified as Pathogenic.

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