ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.485_486GA[1] (p.Glu163fs) (rs730881708)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410607 SCV000486096 likely pathogenic Fanconi anemia, complementation group C 2016-03-29 criteria provided, single submitter clinical testing
GeneDx RCV000160466 SCV000211031 likely pathogenic not provided 2018-10-17 criteria provided, single submitter clinical testing This deletion of four nucleotides is denoted FANCC c.487_490delGAGA at the cDNA level and p.Glu163IlefsX30 (E163IfsX30) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CAGA[delGAGA]ATCA. The deletion causes a frameshift, which changes a Glutamic Acid to an Isoleucine at codon 163, and creates a premature stop codon at position 30 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. FANCC c.487_490delGAGA has been reported in at least one individual with ovarian cancer (Susswein 2016). Based on currently available information, we consider this to be a likely pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000410607 SCV000695433 likely pathogenic Fanconi anemia, complementation group C 2017-03-14 criteria provided, single submitter clinical testing Variant summary: The FANCC c.487_490delGAGA (p.Glu163Ilefs) variant results in a premature termination codon, predicted to cause a truncated or absent FANCC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation variant downstream of this position, c.1642C>T (p.Arg548X) has been classified as pathogenic by our laboratory. This variant is absent in 120886 control chromosomes. A publication has reported the variant in a patient diagnosed with OvC, who also carried another pathogenic RAD51C variant, 404+2T>C. In addition, multiple clinical diagnostic laboratories have classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000528984 SCV000626250 pathogenic Fanconi anemia 2018-07-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu163Ilefs*30) in the FANCC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This particular variant has been observed in an individual affected with ovarian cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 182465). Loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). For these reasons, this variant has been classified as Pathogenic.

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