Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001018323 | SCV001179547 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-18 | criteria provided, single submitter | clinical testing | The p.A293V variant (also known as c.878C>T), located in coding exon 8 of the BMPR1A gene, results from a C to T substitution at nucleotide position 878. The alanine at codon 293 is replaced by valine, an amino acid with similar properties. This variant was identified in a cohort of 51 early onset non familial colorectal cancer by exome sequencing (Thutkawkorapin J et al. Mol Genet Genomic Med, 2019 05;7:e605). 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. |
Invitae | RCV001242736 | SCV001415844 | uncertain significance | Juvenile polyposis syndrome | 2022-06-15 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt BMPR1A protein function. ClinVar contains an entry for this variant (Variation ID: 822732). This missense change has been observed in individual(s) with colorectal cancer (PMID: 30809968). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 293 of the BMPR1A protein (p.Ala293Val). |