ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.-1_2del (p.Met1del)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000808740 SCV000948858 likely pathogenic Juvenile polyposis syndrome 2018-11-06 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the BMPR1A mRNA. The next in-frame methionine is located at codon 29. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BMPR1A-related disease. While this variant is expected to result in an absent protein product, possible rescue of translational initiation by the downstream methionine would lead to the disruption of the signal peptide (residues 1-23), which appears critical for BMPR1A-mediated cellular localization (PMID: 23433720). Also, different variants (c.1A>C, c.1A>G) giving rise to a similar protein effect observed here (initiator codon) has been reported in individuals affected with juvenile polyposis syndrome (PMID: 18823382, Invitae), indicating that this residue may be critical for protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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