Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001185731 | SCV001351996 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with proline at codon 171 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 been identified in 1/251150 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. |
Invitae | RCV001206444 | SCV001377752 | uncertain significance | Juvenile polyposis syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 171 of the BMPR1A protein (p.Ser171Pro). This variant is present in population databases (rs377733546, 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: 924435). 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 80%. 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, |
RCV001185731 | SCV002531103 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-15 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV001185731 | SCV002642228 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-08 | criteria provided, single submitter | clinical testing | The p.S171P variant (also known as c.511T>C), located in coding exon 5 of the BMPR1A gene, results from a T to C substitution at nucleotide position 511. The serine at codon 171 is replaced by proline, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |