Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000658573 | SCV000780350 | likely pathogenic | not provided | 2017-12-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000658573 | SCV002208875 | pathogenic | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change affects a splice site in intron 20 of the PDE6C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PDE6C are known to be pathogenic (PMID: 19887631, 23776498, 26103963, 30080950). This variant is present in population databases (rs753310704, gnomAD 0.03%). Disruption of this splice site has been observed in individuals with achromatopsia (PMID: 19615668; Invitae). ClinVar contains an entry for this variant (Variation ID: 8766). 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. |
3billion | RCV002250457 | SCV002521806 | pathogenic | Cone dystrophy 4 | 2022-05-22 | 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: 0.004%). Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. Two affected offsprings share the same variant (3billion dataset). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (3billion dataset). The variant has been reported to be associated with PDE6C related disorder (ClinVar ID: VCV000008766 / PMID: 19615668). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
OMIM | RCV000009311 | SCV000029529 | pathogenic | Achromatopsia 5 | 2019-03-15 | no assertion criteria provided | literature only |