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
27453576 Dias et al (2016) report a unique de novo variant in the BCL11A gene in each of nine individuals with intellectual disability, strabismus, persistence of fetal hemoglobin, and other findings such as joint hypermobility, behavior abnormalities, facial dysmorphism and microcephaly (three missense, three nonsense, and three frameshift). Two of the nonsense variants were in exon 2 of this 4-5 exon gene (depending on transcript). Variants were detected by whole exome sequencing. Functional studies of missense mutations were consistent with loss of function and haploinsufficiency of Bcl11a in mice causes impaired cognition and behavior and microcephaly.
25938782 Basak et al (2015) found BCL11A as the only gene in the smallest region of overlap in three patients with different de novo deletions from 2p15 to 2p16.1, autism, hypotonia, facial dysmorphism, developmental delay, and persistent fetal hemoglobin. Deletions were detected by aCGH.
25979662 Balci et al (2015) report a de novo 0.875 Mb deletion encompassing only BCL11A detected by aCGH in a patient with developmental delay, brain malformations, and dysmorphic features. The entire BCL11A gene is included in the deleted interval and no other significant CNVs were observed in this patient.

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.