ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.1402G>A (p.Glu468Lys)

gnomAD frequency: 0.00001  dbSNP: rs199907158
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000635476 SCV000756890 uncertain significance Juvenile polyposis syndrome 2024-12-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 468 of the BMPR1A protein (p.Glu468Lys). This variant is present in population databases (rs199907158, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 529944). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BMPR1A protein function. 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.
Sema4, Sema4 RCV002258978 SCV002528570 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-30 criteria provided, single submitter curation
Ambry Genetics RCV002258978 SCV002699150 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-04 criteria provided, single submitter clinical testing The p.E468K variant (also known as c.1402G>A), located in coding exon 10 of the BMPR1A gene, results from a G to A substitution at nucleotide position 1402. The glutamic acid at codon 468 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV002258978 SCV004360100 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-04 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 468 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 reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 2/251486 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.
All of Us Research Program, National Institutes of Health RCV000635476 SCV004825244 uncertain significance Juvenile polyposis syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 468 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 reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 2/251486 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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