Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781351 | SCV000919324 | likely pathogenic | Fanconi anemia, complementation group C | 2018-11-16 | criteria provided, single submitter | clinical testing | Variant summary: FANCC c.377_378delGA (p.Arg126IlefsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.520C>T (p.Arg174X), c.553C>T (p.Arg185X), and c.1642C>T (p.Arg548X)). The variant was absent in 246168 control chromosomes. c.377_378delGA has been reported in the literature in individuals affected with Fanconi Anemia Group C (Ameziane_2008, Nalepa_2013), along with two siblings who were heterozygous for the variant and suffered from T-ALL with subsequent MDS transforming to AML in one of them (Rischewski_200). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Leiden Open Variation Database | RCV000781351 | SCV001365290 | pathogenic | Fanconi anemia, complementation group C | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Johan de Winter. |