ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.712C>G (p.Arg238Gly)

dbSNP: rs747728399
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Total submissions: 9
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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 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 238 of the BMPR1A protein (p.Arg238Gly). This variant is present in population databases (rs747728399, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of juvenile polyposis syndrome (PMID: 30680046). ClinVar contains an entry for this variant (Variation ID: 449255). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt BMPR1A function with a positive predictive value of 95%. 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 Diagnostics, LLC DBA Color Health RCV000581103 SCV000682911 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-08 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 238 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with duodenal polyposis in the literature (PMID: 30680046). This variant has been identified in 6/282802 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000520400 SCV001133469 uncertain significance not provided 2018-10-02 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000581103 SCV002531113 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-14 criteria provided, single submitter curation
Ambry Genetics RCV000581103 SCV002665770 benign Hereditary cancer-predisposing syndrome 2021-12-28 criteria provided, single submitter clinical testing This alteration is classified as 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.
PreventionGenetics, part of Exact Sciences RCV003424076 SCV004118197 uncertain significance BMPR1A-related disorder 2023-05-03 criteria provided, single submitter clinical testing The BMPR1A c.712C>G variant is predicted to result in the amino acid substitution p.Arg238Gly. This variant has been reported in an individual with colorectal adenomas (Henn et al. 2019. PubMed ID: 30680046). This variant is reported in 0.0056% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-88676927-C-G) and has conflicting interpretations of benign and uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/449255/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003476215 SCV004212645 uncertain significance Polyposis syndrome, hereditary mixed, 2 2023-06-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000557396 SCV004842883 uncertain significance Juvenile polyposis syndrome 2023-08-08 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 238 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with duodenal polyposis in the literature (PMID: 30680046). This variant has been identified in 6/282802 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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