ClinGen Dosage Sensitivity Curation Page

Xq21.1 population region (DGV_Gold_Standard_June_2021_gssvL136501)

  • Curation Status: Complete
  • id: ISCA-46736
  • Date last evaluated: 2021-08-03
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: Haploinsufficiency unlikely
  • ClinGen Triplosensitivity Score: 0


Location Information

  • Xq21.1
  • GRCh37/hg19 chrX: 76,137,628-76,141,022
  • View: NCBI | Ensembl | UCSC

GRCh37/hg19 chrX: 76,137,628-76,141,022 ()

  • Haploinsufficiency score: Haploinsufficiency unlikely
  • Strength of Evidence (disclaimer): Haploinsufficiency unlikely

Haploinsufficiency phenotype comments:

As part of an effort to identify genomic regions that are unlikely to be dosage sensitive, ClinGen queried the Database of Genomic Variants (DGV) gold standard GRCh37 data set (PMID: 24174537) (downloaded June 2021) for variants meeting the following criteria: passed DGV quality filters, characterized as either a deletion or duplication, >1 kb in size, includes at least one gene, and present at an allele frequency of >5% (with at least 2000 alleles tested). This region corresponds to a variant identified as meeting those criteria in DGV gold standard GRCh37; the DGV gold standard GRCh37 identifier for this variant is reflected in the title for reference. As of July 1st, 2021, there has been no reported relationship between the gene(s) included in this region and human disease. Given the high population frequency, this region has been classified as ?dosage sensitivity unlikely?.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

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

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.