ClinGen Dosage Sensitivity Curation Page
LRP2
- Curation Status: Complete
- id: ISCA-35087
- Date last evaluated: 2019-04-24
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about LRP2 at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/4036
- OMIM: https://omim.org/entry/600073
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK1116/?term=LRP2%5Bgenesymbol%5D
- ClinGen Haploinsufficiency Score: Gene associated with autosomal recessive phenotype
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 1.0
- Haploinsufficiency score: Gene associated with autosomal recessive phenotype
- Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
- Haploinsufficiency Phenotype: DONNAI-BARROW SYNDROME
Haploinsufficiency phenotype comments:
Homozygous and compound heterozygous mutations affecting LRP2 are associated with autosomal recessive Donnai-Barrow syndrome. Kantarci S et al. 2007 PMID: 17632512 reported four unrelated pedigrees with a total of at 6 healthy carrier sibs and 4 healthy carrier parents, who were heterozygous for frameshift mutations. de Ligt J. et al. 2012 PMID: 23033978 Exome sequencing was performed on 100 patients affected with intellectual disability, as well as their healthy parents to identify pathogenic de novo mutations. Although one affected patient was found to have a de novo frameshift mutation in LRP2, the second allele was found to have a paternally inherited missense mutation. Clinical re-evaluation of the proband was consistent with a diagnosis of autosomal recessive Donnai-Barrow syndrome.
- Triplosensitivity score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Triplosensitivity phenotype comment:
No focal duplications of this gene have been reported to be associated with an abnormal phenotype at the time of this review.