ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.686+1G>C

dbSNP: rs1057517125
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001025741 SCV001187988 likely pathogenic Hereditary cancer-predisposing syndrome 2018-11-15 criteria provided, single submitter clinical testing The c.686+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 6 of the FANCC gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. 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 RCV003461410 SCV004196674 likely pathogenic Fanconi anemia complementation group C 2023-05-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003769612 SCV004664050 likely pathogenic Fanconi anemia 2023-08-29 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 826669). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. This variant has not been reported in the literature in individuals affected with FANCC-related conditions. This sequence change affects a donor splice site in intron 7 of the FANCC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). This variant is not present in population databases (gnomAD no frequency).

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