Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282910 | SCV002570905 | likely pathogenic | Fanconi anemia | 2022-07-15 | criteria provided, single submitter | clinical testing | Variant summary: FANCL c.223C>T (p.Gln75X) 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 in ClinVar (e.g. c.739_740dup (p.Met247fs), c.296_297del (p.Gln99fs)). The variant was absent in 251050 control chromosomes (gnomAD). Although c.223C>T has not been reported in the literature in individuals affected with Fanconi Anemia, it has been found in a setting of multigene panel testing in at least one individual with breast cancer (e.g. Tedaldi_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Fanconi Anemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003464431 | SCV004197278 | likely pathogenic | Fanconi anemia complementation group L | 2024-03-11 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002282910 | SCV004276616 | pathogenic | Fanconi anemia | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln75*) in the FANCL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCL are known to be pathogenic (PMID: 19405097, 23613520). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1704583). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV003464431 | SCV005658718 | likely pathogenic | Fanconi anemia complementation group L | 2024-05-09 | criteria provided, single submitter | clinical testing |