ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000009.11) (NC_000009.12)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype

Haploinsufficiency phenotype comments:

PMID 12552564: Auerbach et al 2003, in Human Mutation, described 27 pathogenic, 11 nonpathogenic variants including two common intronic SNPs in FANCG. These findings were described in all 14 exons of FANCG. Among the pathogenic variant was a 10-bp deletion at the beginning of exon14 which is a common Northern European mutation. In this publication, this 10bp deletion was identified in 7 probands either as a homozygous event or in compound heterozygosity with a splice site or small deletion (see Table 5). PMID 15657175: Morgan et al 2005, in journal Blood, using Sanger sequencing for all exons of the FANCG gene identified 4 individuals that were homozygous for a 7-bp deletion in exon 5 of FANCG, c.637_643delTACCGCC. This variant was predicted to produce a truncated protein. Further using a PCR mutation assay, DNA samples from a total of 40 unrelated Fanconi Anemia patients of South African descent were screened for this FANCG deletion. It was present in 33 (82.5%) of 40 (all except 2 being homozygotes) individuals. Most mutation-carrying patients were from tribal regions in South Africa. A founder effect was suggested. In all above publications, no focal deletions of FANCG reported. Of note, ClinVar reports a loss of function 389bp pathogenic deletion encompassing exon 6-7 of the FANCG gene (reported by Invitae, Accession: SCV001196827.1, submitted: Feb 06, 2020). This partial deletion is predicted to create a premature stop codon resulting in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with FANCG-related conditions. Given the well recognized autosomal recessive inheritance of the phenotype (also see ) along with no notable reports in the literature to date of copy number variants overlapping only the FANCG gene (in either DGV gold or disease databases), the gene is not strictly associated with haploinsufficiency

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

Triplosensitivity phenotype comment:

No focal duplications of FANCG reported to date in known literature (Google Scholar search), ClinVar or DGV (accessed June 2020). Occurrence of much larger, megabase sized duplications are enriched in cases vs. controls (Coe et al 2014 study). In gnomAD structural variants dataset (v2.1, accessed Nov. 2020), no duplications noted,