ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.712C>G (p.Arg238Gly) (rs747728399)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520400 SCV000617154 uncertain significance not provided 2017-05-03 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.712C>G at the cDNA level, p.Arg238Gly (R238G) at the protein level, and results in the change of an Arginine to a Glycine (CGG>GGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Arg238Gly was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BMPR1A Arg238Gly occurs at a position that is conserved across species and is located in the Protein Kinase Domain (Howe 2004, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BMPR1A Arg238Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000557396 SCV000632731 uncertain significance Juvenile polyposis syndrome 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 238 of the BMPR1A protein (p.Arg238Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 449255). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV000581103 SCV000682911 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000520400 SCV001133469 uncertain significance not provided 2018-10-02 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.