ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.170C>G (p.Pro57Arg) (rs1057517610)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409902 SCV000489435 uncertain significance Generalized juvenile polyposis/juvenile polyposis coli 2016-10-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000494075 SCV000581497 likely pathogenic Hereditary cancer-predisposing syndrome 2019-10-19 criteria provided, single submitter clinical testing The p.P57R variant (also known as c.170C>G), located in coding exon 2 of the BMPR1A gene, results from a C to G substitution at nucleotide position 170. The proline at codon 57 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in several individuals with juvenile polyposis syndrome (JPS) (Lynch HT et al. Cancer Genet. Cytogenet., 2004 Jan;148:104-17; Howe JR et al. J. Med. Genet., 2004 Jul;41:484-91; Calva-Cerqueira D et al. Clin. Genet., 2009 Jan;75:79-85; Ambry internal data). In one study, bone morphogenetic protein signaling measured by a reporter assay was not reduced for BMPR1A p.P57R compared to wild type; however, subcellular localization was affected with the majority of protein showing intracellular localization as opposed to wild type BMPR1A, which localized solely to the membrane (Howe JR et al. J. Surg. Res., 2013 Oct;184:739-45). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV001358782 SCV000756865 uncertain significance Juvenile polyposis syndrome 2020-10-26 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 57 of the BMPR1A protein (p.Pro57Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with juvenile polyposis (PMID: 15235019, 18823382, 14734220). ClinVar contains an entry for this variant (Variation ID: 371995). An experimental study has reported that this missense change affects the cellular localization of the BMPR1A protein, however, it did not reduce BMP signaling activity in vitro (PMID: 23433720). 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 Health, Inc RCV000494075 SCV000911648 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-04 criteria provided, single submitter clinical testing

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