ClinVar Miner

Submissions for variant NM_001353214.3(DYM):c.1762C>T (p.Arg588Ter)

gnomAD frequency: 0.00001  dbSNP: rs780873164
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001871621 SCV002127590 pathogenic not provided 2023-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg533*) in the DYM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYM are known to be pathogenic (PMID: 12491225, 12554689, 18996921). This variant is present in population databases (rs780873164, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DYM-related conditions. ClinVar contains an entry for this variant (Variation ID: 992365). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001871621 SCV004562653 pathogenic not provided 2023-09-28 criteria provided, single submitter clinical testing The DYM c.1597C>T; p.Arg533Ter variant (rs780873164), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 992365). This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with skeletal dysplasias and are considered pathogenic (Maddirevula 2018, Neumann 2006). Based on available information, the p.Arg533Ter variant is considered to be likely pathogenic. References: Maddirevula S et al. Expanding the phenome and variome of skeletal dysplasia. Genet Med. 2018 Dec;20(12):1609-1616. PMID: 29620724. Neumann LM et al. Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia: clinical and molecular findings in three families supporting genetic heterogeneity in Smith-McCort dysplasia. Am J Med Genet A. 2006 Mar 1;140(5):421-6. PMID: 16470731.
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV001280803 SCV001468137 likely pathogenic Dyggve-Melchior-Clausen syndrome 2020-06-16 no assertion criteria provided clinical testing

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