Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003468186 | SCV004197276 | likely pathogenic | Fanconi anemia complementation group L | 2023-02-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003523190 | SCV004300757 | likely pathogenic | Fanconi anemia | 2023-09-28 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the PHD/RING finger domain of the FANCL protein, which is necessary for FANCL interaction with Ube2t and Ube2w, and subsequent monoubiquitination of FANCD2 (PMID: 12973351, 17938197, 19111657, 24389026, 26149689). While functional studies have not been performed to directly test the effect of this variant on FANCL protein function, this suggests that disruption of this region of the protein is causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with FANCL-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Ser348Asnfs*2) in the FANCL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 28 amino acid(s) of the FANCL protein. |
| Fulgent Genetics, |
RCV003468186 | SCV005658665 | likely pathogenic | Fanconi anemia complementation group L | 2024-05-16 | criteria provided, single submitter | clinical testing |