ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
17522144 Mutation analysis on a cohort of 120 patients with congenital eye anomalies identified 12 cases with heterozygous SOX2 mutations; 5 whole gene deletions, 1 partial deletion, and 6 intragenic mutations are reported.
16543359 Heterozygous, loss-of-function SOX2 mutations are identified in three unrelated individuals with Anophthalmia-Esophageal-Genital (AEG) syndrome (MIM# 600992). One case of a 2.7 Mb deletion encompassing SOX2 and associated with a cryptic translocation t(3;7)(p28;p21.3) is described. The other two have a SOX2 nonsense or missense mutation.
12612584 A deletion containing SOX2 was identified at the 3q breakpoint in a child with t(3;11)(q26.3;p11.2) associated with bilateral anophthalmia

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.