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
24463507 Fromer M et al. (2014) Large whole exome sequencing study of de novo mutations in schizophrenia to date, based upon genomic (blood) DNA from 623 schizophrenia trios. Confirmed de novo frameshift in female (patient ID 2274-1) with schizophrenia (see supplemental). Variant nomenclature not reported.
25363768 Iossifov I et al. (2014) Large whole exome sequencing from more than 2,500 simplex families each having a child with an autistic spectrum disorder (ASD). Confirmed de novo frameshift in male and female sibling (family ID 12473) with ASD (see supplemental). Variant nomenclature not reported, report also includes a de novo missense.
27824329 Wang T et al. (2016) Large sequencing study using single-molecule molecular inversion probes (smMIPs) in 189 risk genes in 1,542 Chinese probands with ASD. Maternally inherited frameshift (ID SKLMG_M08563) (c.3012_*3dup) in proband with ASD, and a maternally inherited missense (ID SKLMG_M21013) (c.2501G>A, p.Arg834Gln) in proband with ASD.

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.