BMPR2 was first reported in relation to autosomal dominant pulmonary arterial hypertension in 2000 (Deng et al PMID:10903931 and The International PPH Consortium PMID:10973254). More than 500 unique variants (missense, in-frame indel, nonsense, frameshift, large deletions) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level, case-control, segregation and experimental data. Summary of case-level data: 12 points. Variants in this gene have been reported in at least 16 probands in 2 publications (PMID:10903931, PMID:10973254). Variants in this gene segregated with disease in 10 additional family members. More evidence is available in the literature but the maximum score for genetic evidence (12 points) has been reached. The mechanism is haploinsufficiency (PMID:11115378, PMID: 16429395). Summary of experimental data: 6 points. This gene-disease association is supported by expression, biochemical, in vitro functional and animal model data. In summary, BMPR2 is definitively associated with autosomal dominant pulmonary arterial hypertension. This has been repeatedly demonstrated in both research and diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen PH Working Group on Sept 9, 2020.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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