ClinGen Dosage Sensitivity Curation Page

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

  • Curation Status: Complete
  • id: ISCA-37498
  • Date last evaluated: 2018-01-26
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 2
  • ClinGen Triplosensitivity Score: 0


Location Information

  • 11q13.2-q13.4
  • GRCh37/hg19 chr11: 67,763,646-71,236,931
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr11: 67,996,175-71,525,885
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000011.9) ()
  • Haploinsufficiency score: 2
  • Strength of Evidence (disclaimer): Some evidence for dosage pathogenicity
Evidence for haploinsufficiency 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.

Haploinsufficiency phenotype comments:

Evidence supporting 11q13.2q13.4 (SHANK2/FGFs) haploinsufficiency is considered to be emerging at this time. There are currently two patients reported in the literature with de novo deletions of this entire region and a third patient (summarized below) with a deletion involving a majority of this region (inheritance unknown). Clinical findings in common include developmental delay, speech delay, intellectual disability, microcephaly, long slender fingers with 5th finger clinodactyly, as well as several dysmorphic craniofacial features. Statistical significance for enrichment of 11q13.2q13.4 deletions amongst patients has not been observed, possibly due to its relative rarity. Therefore the haploinsufficiency score is 2. Additional relevant literature is summarized below: PMID 28018436: Kim et al. (2016) describe a 2.75 Mb deletion (hg38 coordinates chr11:68,000,777-70,748,975) in a 12 month old child with moderate developmental delay, microcephaly, dysmorphic craniofacial features, and delayed dentition. This deletion is smaller than the deletions that are flanked by segmental duplications, but involves both FGF3 and SHANK2. Parental testing was not reported for this patient. PMID 25217958: Coe et al., (2014): In a large-scale case-control comparison study of the relative prevalence of copy number variants in patients with ID/DD, MCA, and other developmental phenotypes compared to controls, 11q13.2q13.4 (SHANK2/FGFs) region deletions were observed in 1/29,085 patients and 0/19,584 controls (p=0.5980). Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

There is currently no evidence to support triplosensitivity of this region; therefore the triplosensitivity score is 0.? Additional relevant literature is summarized below: PMID 25217958: Coe et al., (2014): In a large-scale case-control comparison study of the relative prevalence of copy number variants in patients with ID/DD, MCA, and other developmental phenotypes compared to controls, 11q13.2q13.4 (SHANK2/FGFs) region duplications were observed in 0/29,085 patients and 0/19,584 controls (p=1.0000). Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.