ClinVar Miner

Submissions for variant NM_001204.7(BMPR2):c.1459G>T (p.Asp487Tyr) (rs863223421)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199780 SCV000249644 likely pathogenic not provided 2014-06-30 criteria provided, single submitter clinical testing p.Asp487Tyr (GAT>TAT): c.1459 G>T in exon 11 of the BMPR2 gene (NM_001204.6). The D487Y variant that is likely pathogenic was identified in the BMPR2 gene. It has not been published as a mutation or as a benign polymorphism to our knowledge. The D487Y variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In addition, the D487Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Moreover, this substitution occurs at a position that is completely conserved across species in well conserved region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. A variant in this residue (D487V) has been reported previously in association with PAH (Pfarr N et al., 2011). Furthermore, additional missense mutations in nearby residues (C483R, D485G, A490V, R491W, R491Q) have been reported in association with PAH, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. This variant was found in PAH-ARRHYTHMIA

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