Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000190586 | SCV000245610 | likely pathogenic | Fanconi anemia complementation group F | 2014-12-05 | criteria provided, single submitter | clinical testing | The p.Gly231GlufsX7 variant in FANCF has not been previously reported in individuals with Fanconi anemia and data from large population studies is insufficient to assess the frequency of this variant. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 231 and leads to a premature termination codon 7 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Complete loss of FANCF function has been identified in several individuals with Fanconi anemia (complementation group F; de Winter 2000, Chandra 2005). In summary, although additional studies are required to fully establish its clinical significance, the p.Gly231GlufsX7 variant is likely pathogenic. |
| Invitae | RCV002517907 | SCV003238065 | likely pathogenic | Fanconi anemia | 2022-05-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly231Glufs*7) in the FANCF gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 144 amino acid(s) of the FANCF protein. This variant is present in population databases (rs747622521, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FANCF-related conditions. ClinVar contains an entry for this variant (Variation ID: 208581). This variant disrupts the C-terminus of the FANCF protein, which is important for proper protein interaction of the FA complex. Experimental studies have shown that disruption of the C-terminus affects FANCF protein function (PMID: 12649160, 11063725, 15262960, 17082180). 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. |