ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000008.10) (NC_000008.11)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
28263302 Yuen et al (2017) - MSSNG project, genome seq, autism study, 2,066 families, one de novo LOF in RB1CC1 (exon 23)
21822266 Xu et al (2011) - exomes, schizophrenia study, 53 family trios with SCZ proband, 22 unaffected trios. One de novo LOF in RB1CC1 (exon 15).

Haploinsufficiency phenotype comments:

While there is some evidence for haploinsufficiency, the two studies have different although related phenotypes and therefore this will be scored as 1 pending further evidence.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for gain of function phenotype
PubMed ID Description
26151896 Degenhardt et al (2013) - CNV analysis of existing SNP array data, schizophrenia study (caucasian), only looked at 55 candidate genes. Discovery cohort: 1637 SCZ inpatient cases & 1627 "controls" (major depressive disorder patients). Replication cohort: 6824 cases & 111,244 controls from a number of studies. (3111 patients and 2267 controls from the International Schizophrenia Consortium, 1564 patients and 6944 controls from the Welcome Trust Case Control Consortium, 604 patients and 497 controls from Munich, Germany, 834 Dutch patients and 672 controls, 711 patients and 100 864 population-based controls from deCODE genetics.) Different platforms used. Duplications of RB1CC1 were found to be associated with SCZ (P=1.29 ? 10?5; odds ratio=8.58). Duplicated in 5/1637 (0.3%) patients and 1/1627 (0.06%) control in the discovery cohort. Duplicated in 4/6824 (0.06%) patients and 11/111,244 (0.01%) controls in replication cohort. However, overall, only 2/8461 (0.02%) cases and 1/112 871 (0.001%) control have RB1CC1 only duplication. Others all overlap with FAM150A (this gene is not well characterised). Furthermore, one of the two cases with RB1CC1 only duplication has a breakpoint within the gene. Therefore this leave one case and one control with RB1CC1 duplication for. purposes of assessing triplosensitivity. We do not know the inheritance status of the duplications.
21841781 Cooper et al (2011) - "copy number variation morbidity map" generated from arrays (CGH) of 15,767 children with various developmental and intellectual disabilities, compared CNVs (SNP array) from 8,329 adult controls from dbGaP GWAS studies. 7 cases with duplication but none of these are RB1CC1-only, most also include NPBWR1. 1 case is inherited and rest have unknown inheritance. 1 additional case with an inherited dup is mentioned as being present in Decipher (one breakpoint within RB1CC1 and also includes NPBWR1).

Triplosensitivity phenotype comment:

Due to there being only a single case of RB1CC1-only, whole gene duplication and no inheritance information, will leave this with a zero score, pending further evidence. Note that the CNV breakpoints in the two studies (PMID 26151896 & 21841781) are different.