Sarcoma susceptibility

Gene: FANCC

Updating tags to be Q3_22_expert_review and Q3_22_rating so that gene is included in the next GMS report (Oct 2022)

Created: 5 Oct 2022, 5:20 p.m. | Last Modified: 5 Oct 2022, 5:20 p.m.

Panel Version: 1.72

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Expert review indicated that there is not sufficient evidence for this gene-disease association at this time.

Created: 30 Jan 2023, 11:26 a.m. | Last Modified: 30 Jan 2023, 11:26 a.m.

Panel Version: 1.73

Comment on list classification: Rating Amber but will flag this gene for GMS review to determine whether there is enough evidence supporting contribution of germline variants in FANCC to sarcoma pathogenesis.

Gillani et al., (2022) reported statistically significant enrichment for predicted pathogenic germline variants in the FANCC gene in a cohort of European Ewing sarcoma patients. However, variants have reduced penetrance and the overall frequency of these variants was low (1.5% in discovery cohort, 0.8% in validation cohort).
Chan etl al., (2017) also identified another likely pathogenic frameshift deletion in FANCC in an individual with epitheloid sarcoma

Created: 22 Jun 2022, 11:15 a.m. | Last Modified: 22 Jun 2022, 11:15 a.m.

Panel Version: 1.71

Green List (high evidence)

At least 6 individuals in PMID: 35512711 with significant enrichment (OR=12 and 7 in discovery and validation cohorts, respectively)
Sources: Literature

Created: 9 May 2022, 7:24 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ewing Sarcome

Publications

• PMID: 35512711