Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ocular Genomics Institute, |
RCV001376465 | SCV001573616 | likely pathogenic | Cone-rod dystrophy and hearing loss 1 | 2021-04-08 | criteria provided, single submitter | research | The CEP78 c.1450C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. |
| Labcorp Genetics |
RCV001390855 | SCV001592720 | pathogenic | not provided | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg484*) in the CEP78 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP78 are known to be pathogenic (PMID: 27588451, 27588452, 27627988). 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 not been reported in the literature in individuals affected with CEP78-related conditions. ClinVar contains an entry for this variant (Variation ID: 1065756). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Broad Center for Mendelian Genomics, |
RCV003225969 | SCV003922274 | likely pathogenic | Cone-rod dystrophy and hearing loss | 2023-05-02 | criteria provided, single submitter | curation | The heterozygous p.Arg484Ter variant in CEP78 was identified by our study, in the compound heterozygous state with a likely pathogenic variant (hg38 chr9:78235965_78243734del), in one individual with cone-rod dystrophy. This individual also carried a likely pathogenic variant (hg38 chr9:78235965_78243734del), however the phase of these variants are unknown at this time. The p.Arg484Ter variant in CEP78 has not been previously reported in the literature in individuals with cone-rod dystrophy and hearing loss 1 but has been identified in 0.01% (1/8014) of African/African American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP: rs1210581905). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID: 1065756) and has been interpreted as pathogenic by Invitae and as likely pathogenic by the Massachusetts Eye and Ear Ocular Genomics Institute. This nonsense variant leads to a premature termination codon at position 484, which is predicted to lead to a truncated or absent protein. Loss of function of the CEP78 gene is an established disease mechanism in autosomal recessive cone-rod dystrophy and hearing loss 1. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive cone-rod dystrophy and hearing loss 1. ACMG/AMP Criteria applied: PVS1, PM2_Supporting (Richards 2015). |
| OMIM | RCV001376465 | SCV005387715 | pathogenic | Cone-rod dystrophy and hearing loss 1 | 2024-10-30 | no assertion criteria provided | literature only |