ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000019.9) (NC_000019.10)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Several studies (23263490; Palles et al. 2013 24501277; Valle et al 2014 25529843; Spier et al. 2015 25559809 ; Chubb et al. 2015 26133394; Bellido et al. 2016 26648449; Jansen et al. 2015 28306219; Ferrer et al. 2017) report association of missense mutations in POLD1 (mainly in the exonuclease domain) and early-onset colon cancer and/or colon polyposis. There is emerging evidence that some exonuclease domain missense mutations cause a drastic decrease in fidelity of exonuclease activity for POLD1. However, single gene deletions of POLD1, or deletions of exons and truncating mutations occurring outside the exonuclease domain, are not as commonly reported. Functional evidence of the impact of these mutations (other than missense exonuclease domain mutations) is sparse. POLD1 was scored based on secondary evidence seen in ClinVar, with >10 submissions of POLD1 displaying substantial, multi-exon or frameshift deletions reported in the disease of colorectal cancer. However, the interpretations are mainly Uncertain due to a lack of publications on deletions and variants outside the exonuclease domain.

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

Triplosensitivity phenotype comment:

no evidence for triplosensitivity