ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1327C>T (p.Arg443Cys) (rs35619497)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000586369 SCV000166528 benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130683 SCV000185570 benign Hereditary cancer-predisposing syndrome 2014-12-09 criteria provided, single submitter clinical testing
GeneDx RCV000120251 SCV000209877 likely benign not specified 2018-01-12 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.
Illumina Clinical Services Laboratory,Illumina RCV000285657 SCV000365653 likely benign Juvenile Polyposis 2016-06-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120251 SCV000593652 uncertain significance not specified 2016-07-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120251 SCV000600214 uncertain significance not specified 2017-04-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586369 SCV000698311 likely benign not provided 2016-05-27 criteria provided, single submitter clinical testing Variant summary: The c.1327C>T in BMPR1A gene is a missense change that involves the alteration of a highly conserved nucleotide and 5/5 in silico tools predict deleterious outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.061%, predominantly in individuals of European and Latino origins (0.08% and 0.13%, respectively). These frequencies exceed the maximal expected allele frequency for a pathogenic variant in BMPR1A (0.0002%). The variant of interest has been reported via reputable database/clinical laboratories as VUS/Benign without evidence to independently evaluate. On the other hand, the variant was identified in JP pt, who reportedly carried a known germline pathogenic mutation in SMAD4 and functional studies showed that R443C expression and BMP signaling levels comparable to wild-type, but it was mislocalized in transfected cells. One other publication reports the variant to co-occur in a patient with a potential pathogenic MSH2 mutation, and an internal sample has a co-occurrence with a pathogenic PMS2 variant, c.2186_2187delTC (classified as pathogenic by LCA). Taken together, this variant has been classified as a Likely Benign.
Counsyl RCV000123222 SCV000784746 likely benign Juvenile polyposis syndrome 2017-12-22 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000586369 SCV000806597 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing
Color RCV000130683 SCV000910565 likely benign Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing
ITMI RCV000120251 SCV000084401 not provided not specified 2013-09-19 no assertion provided reference population
CSER_CC_NCGL; University of Washington Medical Center RCV000123222 SCV000190074 uncertain significance Juvenile polyposis syndrome 2016-08-15 no assertion criteria provided research Originally interpreted based on literature review PMID: 25637381. Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 60 year old with over 20 adenomatous colon polyps and family history of colon cancer.

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