ClinGen Dosage Sensitivity Curation Page

11q13.2q13.4 recurrent region (includes SHANK2, FGFs)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
21373257 Wischmeijer et al. (2010) describe a 3.4 Mb deletion (hg38 coordinates chr11:68,001,284-71,575,789) in a child with dysmorphic features, small teeth, moderate to severe intellectual disability, language delay, and developmental delay. The deletion was flanked by inverted homologous segmental duplications, and is a region predicted by Sharp et al (2006) to be susceptible to LCR mediated copy number variation (PMID: 16906162). Parental testing revealed that the deletion was de novo and that it occurred on the maternally-derived chromosome 11.
28211979 Marcou et al. (2016) describe a 3.5 Mb deletion (hg38 coordinates chr11:68,031,693-71,593,495) in a child with moderate to severe intellectual disability, language delay, developmental delay, feeding difficulty, microcephaly, dysmorphic craniofacial features, widely spaced teeth, long slender fingers with 5th finger clinodactyly, and additional clinical findings. Parental FISH testing was performed revealed that this deletion was de novo.

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.