Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000616574 | SCV000712081 | likely pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies | 2016-05-15 | criteria provided, single submitter | clinical testing | The p.Arg505X variant in UNC80 has not been reported in the literature, and has been identified in 1/21528 chromosomes by the Exome Aggregation Consortium (ExAC , http://exac.broadinstitute.org). Although this variant has been seen in the ge neral population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 505, which is predicted to lead to a truncated or absent protein. Bi allelic loss of function of the UNC80 gene has been associated with Infantile hy potonia with psycho-motor retardation and characteristic facies-2 (Shamseldin 20 16, Stray-Pedersen 2016). In summary, although additional studies are required t o fully establish its clinical significance, the p.Arg505X variant is likely pat hogenic. |
| Labcorp Genetics |
RCV001868020 | SCV002136811 | pathogenic | not provided | 2023-03-26 | criteria provided, single submitter | clinical testing | 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 disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 505011). This variant has not been reported in the literature in individuals affected with UNC80-related conditions. 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 sequence change creates a premature translational stop signal (p.Arg505*) in the UNC80 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UNC80 are known to be pathogenic (PMID: 26545877, 26708751, 26708753). |
| Ce |
RCV001868020 | SCV002496630 | pathogenic | not provided | 2022-01-01 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV003152719 | SCV003841571 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. This homozygous variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000505011). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |