ClinGen Dosage Sensitivity Curation Page

PAFAH1B1

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
11754098 Cardoso et al. (2002) provide a variant update on PAFAH1B1 (LIS1), including intragenic variants from 41 patients with lissencephaly (4 from the current report and others from previous publications). Thirty-six of the 41 variants "result in a truncated or internally deleted protein." Six de novo nonsense variants are included in this publication.
19667223 Saillour et al. (2009) describe 31 heterozygous PAFAH1B1 variants and 8 small intragenic deletions in individuals with lissencephaly. Of the 31 point variants, 12 were nonsense, 8 were frameshift, and 5 were splicing defect variants. The 8 intragenic deletions ranged from 1 exon to almost the entire gene (exons 2-11).

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.