ClinGen Dosage Sensitivity Curation Page
NELFA
- Curation Status: Complete
- id: ISCA-11248
- Date last evaluated: 2012-09-06
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about NELFA at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/7469
- OMIM: https://omim.org/entry/606026
- ClinGen Haploinsufficiency Score: 0
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 0.167
- See related regions:
- 4p16.3 terminal (Wolf-Hirshhorn syndrome) region
- Haploinsufficiency score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Haploinsufficiency phenotype comments:
While haploinsufficiency for WHSC2 alone has not been demonstrated, deletions involving the larger 4p16.3 region cause the contiguous gene deletion disorder, Wolf-Hirschhorn syndrome (WHS) (MIM #194190). The patient described by Rauch et al., 2001 [PMID 11252005] had a de novo deletion of WHSC2 along with a few additional genes, making it one of the most focal deletions involving WHSC2 to date, still the involvement of additional gene complicates any conclusion of WHSC2 haplosensitivity. The patient did not meet all the clinical criteria for WHS, but did present with speech delay, low body weight for height, and minor facial anomalies. As deletions involving the larger Wolf-Hirschhorn region have a haploinsufficiency rating of 3, any deletion involving WHSC2 should be considered carefully for pathogenicity, keeping in mind that the haplosensitivity of WHSC2 alone is not understood.
- Triplosensitivity score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Triplosensitivity phenotype comment:
In a study comparing a large cohort of children with ID and/or DD to unaffected adult controls, the incidence of observed gains of WHSC2 was 7/15,767 cases vs 0/8,329 controls [PMID 21841781], however these duplications were non-focal and included additional genes. Thus the potential pathogenicity of increased WHSC2 gene dosage is currently unknown.