ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
11381269 Howe et al. (2001) identified four BMPR1A germline truncation pathogenic variants in four juvenile polyposis kindreds. Genomic sequencing of BMPR1A in each of these juvenile polyposis kindreds disclosed these truncation pathogenic variants in all affected kindred members but not in normal individuals (figure 2). Individual Case Evidence: Segregation Among Similarly Affected Family Members ? NM_004329.2(BMPR1A):c.44_47delTGTT (p.Leu15Serfs) ? NM_004329.2(BMPR1A):c.715C>T (p.Gln239Ter) ? NM_004329.2(BMPR1A):c.812G>A (p.Trp271Ter) ? NM_004329.2(BMPR1A):c.961del (p.Phe320_Leu321insTer)
15235019 Howe et al (2004) performed a large cohort study including a total of 77 Juvenile polyposis (JP) cases. Germline BMPR1A gene pathogenic variants were identified in 16 cases (20.8%). These included ten truncation (including nonsense and deletion) variants and six missense mutations. Individual Case Evidence: Unknown Inheritance, total 10 cases
23399955 Ngeow et al (2013) performed a large prospective, referral-based study of 603 patients with moderate-load colorectal polyps. Twenty cases (3.3%) were identified carrying a BMPR1A pathogenic variants including twelve BMPR1A focal deletion and/or truncation variants and eight misssense variatns. All the BMPR1A pathogenic variants carriers were diagnosed with Juvenile polyposis and/or other types of cancers (supplementary table). Individual Case Evidence: Unknown Inheritance, total 12 cases

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.