Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001045374 | SCV001209220 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile2385*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). 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 CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 842877). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002497383 | SCV002801994 | likely pathogenic | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2021-12-13 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003467739 | SCV004216507 | likely pathogenic | Bardet-Biedl syndrome 14 | 2024-03-07 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004768808 | SCV005380860 | pathogenic | Meckel syndrome, type 4 | 2024-08-08 | criteria provided, single submitter | clinical testing | Variant summary: CEP290 c.7153delA (p.Ile2385X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.6e-06 in 232328 control chromosomes. To our knowledge, no occurrence of c.7153delA in individuals affected with Meckel Syndrome Type 4 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 842877). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Prevention |
RCV004536082 | SCV004738915 | likely pathogenic | CEP290-related disorder | 2024-02-02 | no assertion criteria provided | clinical testing | The CEP290 c.7153delA variant is predicted to result in premature protein termination (p.Ile2385*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0024% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in CEP290 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |