ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1243G>A (p.Glu415Lys) (rs140592056)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115826 SCV000187390 likely benign Hereditary cancer-predisposing syndrome 2017-10-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034700 SCV000043147 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
CSER_CC_NCGL; University of Washington Medical Center RCV000148376 SCV000190073 likely benign Gastrointestinal polyposis 2014-06-01 no assertion criteria provided research
Color RCV000115826 SCV000537412 likely benign Hereditary cancer-predisposing syndrome 2016-05-19 criteria provided, single submitter clinical testing
Counsyl RCV000119185 SCV000786169 likely benign Juvenile polyposis syndrome 2018-03-12 criteria provided, single submitter clinical testing
GeneDx RCV000120252 SCV000149735 likely benign not specified 2017-12-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ITMI RCV000120252 SCV000084402 not provided not specified 2013-09-19 no assertion provided reference population
Illumina Clinical Services Laboratory,Illumina RCV000380077 SCV000365652 likely benign Juvenile Polyposis 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034700 SCV000698308 benign not provided 2016-09-02 criteria provided, single submitter clinical testing Variant summary: The BMPR1A c.1243G>A (p.Glu415Lys) variant involves the alteration of a conserved nucleotide. Glu415Lys occurs at a position that is conserved across mammals and is located in the protein kinase domain, and 4/5 in silico tools predict a damaging outcome for this variant. This variant was found in 87/122544 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0011238 (75/66740). This frequency is about 562 times the estimated maximal expected allele frequency of a pathogenic BMPR1A variant (0.000002), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. This variant was also observed in three individuals with a history of moderate-load polyposis; reported pathology included hyperplastic, hamartomatous, juvenile and adenomatous polyps (Ngeow 2013); and in one individual undergoing hereditary panel testing for a personal and/or family history suspicious for Lynch syndrome (Yurgelun 2015). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance or likely benign. Taken together and based on the prevalence in the general population, this variant is classified as benign.
Invitae RCV000119185 SCV000153921 benign Juvenile polyposis syndrome 2018-01-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000120252 SCV000538421 uncertain significance not specified 2016-10-31 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is present in HGMD in 5 papers, with comments suggesting likely benign. The variant is present in ExAC at a Max MAF of 0.11% and at 1.6% (165) of Ashkenazi alleles in gnomAD - frequency too high for disease. It is classified as Likely Benign by 4 submitters (GeneDx, Invitae, Ambry, CSER_CC_NCGL) and as VUS by Biesecker lab.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000034700 SCV000778627 likely benign not provided 2018-01-24 no assertion criteria provided clinical testing
PreventionGenetics RCV000034700 SCV000806596 likely benign not provided 2017-12-27 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000115826 SCV000787887 likely benign Hereditary cancer-predisposing syndrome 2017-09-13 no assertion criteria provided clinical testing

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