ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000006.11) (NC_000006.12)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype

Haploinsufficiency phenotype comments:

FANCE is associated with an autosomal recessive Fanconi anemia phenotype and is located on chromosome 16p13.3. Clinical manifestations of Fanconi anemia are diverse and variable. FANCE is a morbid OMIM disease gene. The following captures well established studies describing patients with variants in this gene 1. PMID 11001585: de Winter et al., 2000 (AJHG) performed mutation screening, 3 patients with Fanconi anemia. They were of Turkish and Bangladeshi ethnicity and were identified to harbor separate homozygous mutations in FANCE (Table 1). Two of these mutations were nonsense changes and one was a splice site change creating an inframe stop codon. Parents and unaffected sibling were found to be heterozygous carriers for the nonsense mutations. No overt phenotype was reported in the carriers. 2. PMID 17924555: Ameziane et al, 2008 in Human Mutation performed mutation screening by DHPLC followed by Sanger sequencing. The authors report on two separate homozygous alterations resulting in nonsense variants in FANCE from Fanconi anemia patients. A third alteration was found on one allele and mutation on remaining allele was not detected (Table 1). 3. PMID 31586946: Bogliolo et al., 2020 (Journal of Med Gen) report on one of the largest series of undefined FA patients analyzed by exome sequencing. A novel heterozygous frameshift variant was detected in FANCE (c.929dupC) in one individual. A putative second mutation was not detected in this individual (see Table 1). Taken together, these studies suggest that there is no increased risk reported to develop cancer or another type of disease among Fanconi anemia heterozygotes or mutation carriers (PMID: 22778927). Of note, no deletions involving FANCE or focal deletions of this gene longer than 500bp reported in ClinVar. No deletions reported in DECIPHER. One deletion, 78 kb, involving FANCE and 5 adjacent genes reported in DGV (nsv602910; Cooper et al. 2011) among individuals in the healthy population. In gnomAD, the pLI score is reported as 0 (62.04 in DECIPHER) with several loss of function (LoF) variants reported across the gene (no homozygotes reported for LoF); this data does not support a model for haploinsufficiency.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No focal duplications of FANCE reported in ClinVar or DGV (accessed June 2020). In gnomAD structural variants dataset (v2.1, accessed June 2020), partial duplications involving only a portion of FANCE have been recorded in the healthy population.