ClinGen Dosage Sensitivity Curation Page
FLNB
- Curation Status: Complete
- id: ISCA-18155
- Date last evaluated: 2013-07-25
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about FLNB at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/2317
- OMIM: https://omim.org/entry/603381
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK2534/?term=FLNB
- ClinGen Haploinsufficiency Score: 0
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 0.002
- Haploinsufficiency score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Haploinsufficiency phenotype comments:
Krakow D et al. 2004 PMID: 14991055 Nonsense mutations affecting both alleles of FLNB have been shown to cause autosomal recessive spondylocarpotarsal synostosis syndrome (OMIM 272460). This study also identified autosomal dominant missense mutations or in-frame deletions are associated with a spectrum of skeletal dysplasias which include atelosteogenesis (AO) type I (OMIM 108720), atelosteogenesis type III (OMIM 108721) and Larsen syndrome (OMIM 150250). Bicknell LS et al. 2005 PMID: 15994868 identified heterozygous missense mutations of FLNB in patients with autosomal dominant boomerang dysplasia (OMIM 112310). Per GeneReviews, the "Larsen syndrome ? AO spectrum of conditions...are caused by normal expression of a structurally abnormal FLNB protein. " There is no evidence at this time to suggest that loss of a single copy of FLNB causes an abnormal phenotype. As such, we are giving this gene a score of 0 (in relation to the autosomal dominant phenotypes), and intend to reevaluate if additional evidence becomes available.
- Triplosensitivity score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Triplosensitivity phenotype comment:
At the time of this review, there is no evidence to suggest focal duplications of this gene cause an abnormal phenotype.