Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003034449 | SCV003324960 | pathogenic | Fanconi anemia | 2021-12-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 33 of the FANCA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. Disruption of this splice site has been observed in individual(s) with Fanconi anemia (PMID: 24989076). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FANCA protein in which other variant(s) (p.Arg1117Gly) have been determined to be pathogenic (PMID: 9371798, 10373536, 22778927, 24349332). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Studies have shown that disruption of this splice site results in skipping of exon 34, but is expected to preserve the integrity of the reading-frame (PMID: 24989076). |