Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001091344 | SCV001247312 | pathogenic | not provided | 2018-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001862693 | SCV002201732 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the CEP290 mRNA. The next in-frame methionine is located at codon 11. This variant is present in population databases (rs368984997, gnomAD 0.0009%). Disruption of the initiator codon has been observed in individuals with Leber congenital amaurosis and/or Senior-Loken syndrome (PMID: 17345604, 21866095). ClinVar contains an entry for this variant (Variation ID: 871409). This variant disrupts the p.Trp7 amino acid residue in CEP290. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16682970, 27422788). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV002482162 | SCV002785969 | likely pathogenic | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2022-04-23 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004536141 | SCV004713632 | pathogenic | CEP290-related disorder | 2023-10-27 | criteria provided, single submitter | clinical testing | The CEP290 c.2T>A variant is predicted to disrupt the translation initiation site (Start Loss). This variant was reported in individuals with Leber congenital amaurosis (Patient 416 in Perrault et al. 2007. PubMed ID: 17345604; Supplemental Table 1 in Weisschuh et al. 2020. PubMed ID: 32531858; Table S2 in Drivas et al. 2015. PubMed ID: 26062849) and in a patient with renal and ophthalmic features (Patient 63 in Best et al. 2022. PubMed ID: 35764379). This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88535083-A-T) and has been interpreted as likely pathogenic and pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/871409/). Of note, a different variant that disrupts the methionine start codon (c.1A>G) has also been reported in patients with CEP290-related disorders (Patient F57 in Helou. 2007. PubMed ID: 17617513). Based on this evidence, we interpret the c.2T>A (start loss) variant as pathogenic. |