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
18521840 Poelmans et al., detected a deletion on 21q22.3 containing four genes (PCNT, DIP2A, S100B, and PRMT2) in a family. The deletion cosegregated with dyslexia in a father and his three sons.
25363768 Iossifov et al. reported the detection of a de novo nonsense variant (21:47957426:G:A) and a de novo frameshift variant (21:47958429:A:ACTGGTCT) in the male probands of two autism families (Simons simplex collection ID 13106 and 13012 respectively). The unaffected siblings did not have the same variants. The two de novo variants were identified among 2517 autism families. The frameshift variant was reported in an earlier paper by the same first author (PMID: 22542183)
24643514 Egger etal. reported a ASD patient with a de novo 2.9Mb deletion at 21q22.3 (chr21:43,994,161-46,921,385) involving DIAP2A gene. There are about 100 refSeq genes at this interval.

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.