ClinVar

Description

This variant is denoted BMPR1A c.65A>C at the cDNA level, p.Gln22Pro (Q22P) at the protein level, and results in the change of a Glutamine to a Proline (CAA>CCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Gln22Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BMPR1A Gln22Pro occurs at a position that is not conserved and is located in the signal peptide region (Howe 2004, UniProt). While protein-based in silico analyses are inconsistent regarding the effect this variant may have on protein structure and function, multiple splicing models predict that this variant may lead to the creation of a cryptic splice acceptor site. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether BMPR1A Gln22Pro is pathogenic or benign. We consider it to be a variant of uncertain significance.