Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV002227368 | SCV002506267 | uncertain significance | Asphyxiating thoracic dystrophy 3 | 2022-02-11 | criteria provided, single submitter | clinical testing | The DYNC2H1 c.10627-14A>G variant (rs989023092), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only found on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a highly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic acceptor splice site, that if used, would cause a frameshift. However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time. |
| Gene |
RCV002243530 | SCV002513123 | likely pathogenic | not provided | 2022-04-08 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing |
| Fulgent Genetics, |
RCV002227368 | SCV005680474 | likely pathogenic | Asphyxiating thoracic dystrophy 3 | 2024-02-29 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV005095789 | SCV005774375 | pathogenic | Jeune thoracic dystrophy | 2024-02-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 70 of the DYNC2H1 gene. It does not directly change the encoded amino acid sequence of the DYNC2H1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. 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 has been observed in individual(s) with short-rib thoracic dysplasia type III (PMID: 36442996). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1679489). Studies have shown that this variant alters DYNC2H1 gene expression (PMID: 36442996). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 36442996). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |