ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.478A>G (p.Met160Val) (rs145101532)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129348 SCV000184112 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000129348 SCV000682896 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-11 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763676 SCV000894556 uncertain significance Juvenile polyposis syndrome; Hereditary mixed polyposis syndrome 2 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000656783 SCV000564703 uncertain significance not provided 2018-06-26 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.478A>G at the cDNA level, p.Met160Val (M160V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant was identified via multi-gene panel testing in an individual with colon cancer, as well as individuals with a personal and/or family history of unspecified cancers (Cabanillas 2017, Mandelker 2017, Yurgelun 2017). BMPR1A Met160Val was observed at an allele frequency of 0.02% (5/30782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). BMPR1A Met160Val is located in the helical region of the trans membrane 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 Met160Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000205803 SCV000259496 uncertain significance Juvenile polyposis syndrome 2018-12-23 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 160 of the BMPR1A protein (p.Met160Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs145101532, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 141022). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481297 SCV000600225 uncertain significance not specified 2017-05-08 criteria provided, single submitter clinical testing

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