ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.166-4_166-1dup

gnomAD frequency: 0.00001  dbSNP: rs746016938
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV004591424 SCV000569812 likely pathogenic not provided 2024-04-15 criteria provided, single submitter clinical testing RNA studies demonstrate aberrant splicing (External communication with Ambry Genetics); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 30676620, 29625052, 29922827, 36451132)
Ambry Genetics RCV001012642 SCV001173121 pathogenic Hereditary cancer-predisposing syndrome 2024-01-25 criteria provided, single submitter clinical testing The c.166-4_166-1dupACAG intronic pathogenic mutation results from a duplication of 4 nucleotides between positions c.166-4 and c.166-1 before intron 1 of the FANCC gene. This alteration has been confirmed to be in trans with another FANCC pathogenic mutation in at least one individual with a personal and/or family history that is consistent with Fanconi anemia (Ambry internal data). In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV001851195 SCV002315156 uncertain significance Fanconi anemia 2023-07-31 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the FANCC gene. It does not directly change the encoded amino acid sequence of the FANCC protein. This variant is present in population databases (rs746016938, gnomAD 0.0009%). This variant has been observed in individual(s) with testicular cancer (PMID: 29625052, 30676620). ClinVar contains an entry for this variant (Variation ID: 420828). 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.
Revvity Omics, Revvity RCV003144281 SCV003833911 uncertain significance Fanconi anemia complementation group C 2021-08-31 criteria provided, single submitter clinical testing

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