ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.943G>A (p.Gly315Arg) (rs730881435)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235117 SCV000209875 uncertain significance not provided 2018-02-15 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.943G>A at the cDNA level, p.Gly315Arg (G315R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>AGA). This variant has been reported in at least one individual with colon cancer (Yurgelun 2017). BMPR1A Gly315Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). BMPR1A Gly315Arg is located in the protein kinase domain (Howe 2004, Uniprot). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BMPR1A Gly315Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000159839 SCV000216905 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000463009 SCV000552856 uncertain significance Juvenile polyposis syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 315 of the BMPR1A protein (p.Gly315Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 182069). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000159839 SCV000688304 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing

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