Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001221372 | SCV001393413 | likely pathogenic | Fanconi anemia | 2021-01-15 | 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). 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. This variant has not been reported in the literature in individuals with FANCC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 10 of the FANCC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Ambry Genetics | RCV002379836 | SCV002688879 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-20 | criteria provided, single submitter | clinical testing | The c.996+1_996+2insAG intronic variant results from an insertion of two nucleotides between positions 996+1 and 996+2 after coding exon 9 of the FANCC gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide region is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Baylor Genetics | RCV003469381 | SCV004196683 | likely pathogenic | Fanconi anemia complementation group C | 2023-03-01 | criteria provided, single submitter | clinical testing |