ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1300G>A (p.Gly434Ser) (rs587780108)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212149 SCV000149736 uncertain significance not provided 2018-07-12 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.1300G>A at the cDNA level, p.Gly434Ser (G434S) at the protein level, and results in the change of a Glycine to a Serine (GGC>AGC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BMPR1A Gly434Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). BMPR1A Gly434Ser is located in the protein kinase domain (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 Gly434Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115827 SCV000218182 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000476402 SCV000552881 uncertain significance Juvenile polyposis syndrome 2018-12-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 434 of the BMPR1A protein (p.Gly434Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 127900). 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212149 SCV001133460 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing

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