Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000498064 | SCV000339179 | pathogenic | not provided | 2016-02-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000473837 | SCV000541577 | likely pathogenic | Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis | 2024-07-22 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 34 of the CEP290 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 CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). This variant is present in population databases (rs760915898, gnomAD 0.01%). 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: 285948). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Gene |
RCV000498064 | SCV000589312 | likely pathogenic | not provided | 2025-03-03 | criteria provided, single submitter | clinical testing | Reported in a patient with developmental delay, infantile spasms, renal cysts and nephronophthisis; however, this patient also had a variant in a candidate gene that may be related to the phenotype (PMID: 30311385); Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30267408, 31964843, 30311385) |
Fulgent Genetics, |
RCV000763313 | SCV000893990 | likely pathogenic | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
UNC Molecular Genetics Laboratory, |
RCV000779117 | SCV001251488 | likely pathogenic | CEP290-related disorder | criteria provided, single submitter | research | The CEP290 c.4437+1G>A (p.?) variant is predicted to disrupt a canonical splice donor site, which may result in an aberrant protein. This variant has not been reported in association with CEP290-related disorders. | |
Revvity Omics, |
RCV000498064 | SCV002017029 | pathogenic | not provided | 2019-09-09 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000498064 | SCV002067301 | likely pathogenic | not provided | 2021-07-20 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the CEP290 gene demonstrated a sequence change in the canonical splice donor site of intron 34, c.4437+1G>A. This sequence change is predicted to disrupt the canonical splice donor site, and affect normal splicing of exon 34. This c.4437+1G>A change does not appear to have been previously described in individuals with CEP290-related disorders. This sequence change has been described in the gnomAD database in the non-Finnish European subpopulation with a low frequency of 0.013% (dbSNP rs760915898). Collectively, this evidence suggests c.4437+1G>A is likely pathogenic, however, functional studies have not been performed to prove this conclusively. |
Natera, |
RCV001271571 | SCV001452836 | likely pathogenic | Leber congenital amaurosis | 2020-09-16 | no assertion criteria provided | clinical testing | |
Prevention |
RCV000779117 | SCV004105717 | likely pathogenic | CEP290-related disorder | 2024-08-27 | no assertion criteria provided | clinical testing | The CEP290 c.4437+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been observed in a large dataset of worldwide populations used to evaluate the frequency or percentage of individuals carrying a disease-causing variant in genes associated with autosomal recessive inherited retinal diseases (IRDs) (Table S3, Hanany et al. 2020. PubMed ID: 31964843). This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Variants that disrupt the consensus splice donor site in CEP290 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |