ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.521+5G>C

gnomAD frequency: 0.00001  dbSNP: rs1301899973
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001315508 SCV001506084 uncertain significance Fanconi anemia 2022-05-05 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the FANCC gene. It does not directly change the encoded amino acid sequence of the FANCC protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1016496). Variants that disrupt 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. 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 RCV002350574 SCV002646661 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-05 criteria provided, single submitter clinical testing The c.521+5G>C intronic variant results from a G to C substitution 5 nucleotides after coding exon 5 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. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001315508 SCV002081257 uncertain significance Fanconi anemia 2019-12-31 no assertion criteria provided clinical testing

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