Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001387748 | SCV001588458 | pathogenic | not provided | 2023-04-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys160*) in the PCARE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCARE are known to be pathogenic (PMID: 20398886, 24339724, 26496393). This premature translational stop signal has been observed in individual(s) with PCARE-related conditions (PMID: 28763557). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 812241). |
Broad Center for Mendelian Genomics, |
RCV003225956 | SCV003922172 | pathogenic | PCARE-related retinopathy | 2023-05-02 | criteria provided, single submitter | curation | The homozygous p.Cys160Ter variant in PCARE was identified by our study in one individual with cone-rod dystrophy. The p.Cys160Ter variant in PCARE has been previously reported in one individual with retinitis pigmentosa 54 (PMID: 28763557). This individual (PMID: 28763557) and the individual identified by our study were homozygotes, which increases the likelihood that the p.Cys160Ter variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 812241) and has been interpreted as pathogenic by Invitae and the Sharon lab of Hadassah-Hebrew University Medical Center. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 160, which is predicted to lead to a truncated or absent protein. Loss of function of the PCARE gene is an established disease mechanism in retinitis pigmentosa 54. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive retinitis pigmentosa 54. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3 (Richards 2015). |
Sharon lab, |
RCV002267749 | SCV001160941 | pathogenic | Cone-rod dystrophy | 2019-06-23 | no assertion criteria provided | research |