Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001854939 | SCV002172374 | uncertain significance | not provided | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg230*) in the CLUAP1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CLUAP1 cause disease. This variant is present in population databases (rs769705065, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of CLUAP1-related conditions (PMID: 28679688). ClinVar contains an entry for this variant (Variation ID: 254178). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Biesecker Lab/Clinical Genomics Section, |
RCV000496978 | SCV000299272 | likely pathogenic | Familial aplasia of the vermis | 2016-09-07 | no assertion criteria provided | research | Exome analysis revealed two alterations in CLUAP1 in an individual with Joubert syndrome. This alteration and NM_015041.2:c.338T>G were determined to be in trans based on parental analysis. Genes known to cause Joubert syndrome are involved in primary cilia function and this alteration in CLUAP1 was shown to have an effect on intraflagellar transport. Additionally, this variant is rare in the ExAC database. This is the first report of alterations in CLUAP1 in an individual with Joubert syndrome and identifying additional Joubert patients with alterations in CLUAP1 will help confirm the pathogenicity of these variants. |