Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001222063 | SCV001394144 | uncertain significance | Juvenile polyposis syndrome | 2024-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 16 of the BMPR1A protein (p.Phe16Tyr). This variant is present in population databases (rs151235720, gnomAD 0.008%). 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: 950370). 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) 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 | RCV002339588 | SCV002639570 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-12 | criteria provided, single submitter | clinical testing | The p.F16Y variant (also known as c.47T>A), located in coding exon 1 of the BMPR1A gene, results from a T to A substitution at nucleotide position 47. The phenylalanine at codon 16 is replaced by tyrosine, an amino acid with highly similar properties. This amino acid position is not well 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. |
All of Us Research Program, |
RCV001222063 | SCV004825670 | uncertain significance | Juvenile polyposis syndrome | 2024-03-28 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with tyrosine at codon 16 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 2/277096 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. |