Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580074 | SCV000682878 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 53 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 not been identified 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. |
Labcorp Genetics |
RCV001853864 | SCV002265593 | uncertain significance | Juvenile polyposis syndrome | 2024-03-19 | 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 53 of the BMPR1A protein (p.Glu53Lys). This variant is not present in population databases (gnomAD no frequency). 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: 489691). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BMPR1A protein function with a negative 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. |
Ambry Genetics | RCV000580074 | SCV002709511 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-04 | criteria provided, single submitter | clinical testing | The p.E53K variant (also known as c.157G>A), located in coding exon 2 of the BMPR1A gene, results from a G to A substitution at nucleotide position 157. The glutamic acid at codon 53 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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. |