ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1348G>A (p.Val450Met) (rs55932635)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130813 SCV000185709 likely benign Hereditary cancer-predisposing syndrome 2017-06-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Invitae RCV000205158 SCV000259992 uncertain significance Juvenile polyposis syndrome 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 450 of the BMPR1A protein (p.Val450Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs55932635, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 142024). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV000130813 SCV000537607 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-21 criteria provided, single submitter clinical testing
GeneDx RCV000657050 SCV000567656 uncertain significance not provided 2018-03-19 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.1348G>A at the cDNA level, p.Val450Met (V450M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant was observed in at least one individual with colorectal cancer (Yurgelun 2017). BMPR1A Val450Met was observed at an allele frequency of 0.05% (8/17,248) in individuals of East Asian ancestry in large population cohorts (Lek 2016). This variant is located in cytoplasmic topological domain and the protein kinase domain (Howe 2004, UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BMPR1A Val450Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000487332 SCV000600217 uncertain significance not specified 2017-02-16 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.