ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.1348G>A (p.Val450Met)

gnomAD frequency: 0.00009  dbSNP: rs55932635
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130813 SCV000185709 likely benign Hereditary cancer-predisposing syndrome 2018-07-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV002228499 SCV000259992 likely benign Juvenile polyposis syndrome 2024-01-18 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000130813 SCV000537607 likely benign Hereditary cancer-predisposing syndrome 2021-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000657050 SCV000567656 uncertain significance not provided 2022-08-10 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in individuals with colorectal, gastric, or breast cancer (Greenman 2007, Yurgelun 2017, Dutil 2019); This variant is associated with the following publications: (PMID: 25980754, 28135145, 21153778, 26659599, 17344846, 30761385, 32068069, 31780696, 27535533)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000657050 SCV000600217 likely benign not provided 2023-05-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000487332 SCV001362963 uncertain significance not specified 2022-09-22 criteria provided, single submitter clinical testing Variant summary: BMPR1A c.1348G>A (p.Val450Met) results in a conservative amino acid change located in the Serine-threonine/tyrosine-protein kinase, catalytic domain (IPR000719) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251480 control chromosomes (gnomAD). The observed variant frequency is approximately 32 fold of the estimated maximal expected allele frequency for a pathogenic variant in BMPR1A causing Juvenile Polyposis Syndrome (2e-06), strongly suggesting that the variant is benign. c.1348G>A has been reported in the literature in individuals affected with colorectal cancer or breast cancer (Yurgelun_2017, Dutil_2019, Kwong_2020). These reports do not provide unequivocal conclusions about association of the variant with Juvenile Polyposis Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters have assessed the variant since 2014: two classified the variant as uncertain significance and four as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Sema4, Sema4 RCV000130813 SCV002528564 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-05 criteria provided, single submitter curation
Mayo Clinic Laboratories, Mayo Clinic RCV000657050 SCV004225286 uncertain significance not provided 2022-12-09 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000657050 SCV004234642 uncertain significance not provided 2023-06-08 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000657050 SCV005042387 uncertain significance not provided 2024-04-01 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000487332 SCV005090863 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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