ClinVar Miner

Submissions for variant NR_003051.4(RMRP):n.220A>G

dbSNP: rs936059863
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000703896 SCV000832822 pathogenic Anauxetic dysplasia 2023-06-05 criteria provided, single submitter clinical testing This variant is also known as c.218A>G. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Studies have shown that this variant alters RMRP gene expression (PMID: 17937437). ClinVar contains an entry for this variant (Variation ID: 580378). This variant has been observed in individual(s) with cartilage-hair hypoplasia (PMID: 14608646, 15780958, 16832578). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781820 SCV000920159 pathogenic Metaphyseal chondrodysplasia, McKusick type 2018-12-08 criteria provided, single submitter clinical testing Variant summary: RMRP n.219A>G (also known as 218A>G) involves the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 8e-06 in 125112 control chromosomes (gnomAD and publications). The variant, n.219A>G, has been reported in the literature in individuals affected with Cartilage-Hair Hypoplasia (Nakashima_2003, Harada_2005). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence showing a 10%-<30% decrease in RNA levels associated with this variant (Nakashima_2007). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002493235 SCV002798549 likely pathogenic Anauxetic dysplasia 1; Metaphyseal chondrodysplasia, McKusick type; Metaphyseal dysplasia without hypotrichosis 2022-05-30 criteria provided, single submitter clinical testing
OMIM RCV000015288 SCV000035547 pathogenic Metaphyseal dysplasia without hypotrichosis 2003-12-15 no assertion criteria provided literature only
Natera, Inc. RCV000781820 SCV002077498 pathogenic Metaphyseal chondrodysplasia, McKusick type 2020-08-14 no assertion criteria provided clinical testing

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