Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000599456 | SCV000710447 | likely pathogenic | not provided | 2018-01-23 | criteria provided, single submitter | clinical testing | The c.3012delA variant in the CEP290 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.3012delA variant causes a frameshift starting with codon Glutamic acid 1005, changes this amino acid to a Asparagine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Glu1005AsnfsX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3012delA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.3012delA as a likely pathogenic variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271536 | SCV002556165 | likely pathogenic | Meckel syndrome, type 4 | 2022-06-24 | criteria provided, single submitter | clinical testing | Variant summary: CEP290 c.3012delA (p.Glu1005AsnfsX6) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 178594 control chromosomes (gnomAD). c.3012delA has been reported in the literature in a compound heterozygous individual affected with Leber Congenital Amaurosis (Di Iorio_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV002532698 | SCV003496860 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1005Asnfs*6) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (PMID: 29053603). This variant is also known as K1004fs. ClinVar contains an entry for this variant (Variation ID: 504139). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003465351 | SCV004216591 | pathogenic | Bardet-Biedl syndrome 14 | 2023-07-20 | criteria provided, single submitter | clinical testing |