ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.214A>G (p.Ile72Val) (rs1064795729)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484198 SCV000571809 uncertain significance not provided 2016-09-27 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.214A>G at the cDNA level, p.Ile72Val (I72V) at the protein level, and results in the change of an Isoleucine to a Valine (ATT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Ile72Val 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 Isoleucine and Valine share similar properties, this is considered a conservative amino acid substitution. BMPR1A Ile72Val occurs at a position that is not conserved and is located in the MH1 cysteine-rich domain (Howe 2004). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BMPR1A Ile72Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000530720 SCV000632709 uncertain significance Juvenile polyposis syndrome 2018-03-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 72 of the BMPR1A protein (p.Ile72Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. 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. ClinVar contains an entry for this variant (Variation ID: 422358). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000776272 SCV000911548 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing

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