Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001307465 | SCV001496879 | uncertain significance | Fanconi anemia | 2020-03-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 of the FANCC gene. It does not directly change the encoded amino acid sequence of the FANCC protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FANCC-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002411985 | SCV002675890 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | The c.843+5G>T intronic variant results from a G to T substitution 5 nucleotides after coding exon 7 in the FANCC gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |