Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001318992 | SCV001509716 | uncertain significance | Juvenile polyposis syndrome | 2017-01-18 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BMPR1A-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This sequence change replaces tyrosine with phenylalanine at codon 176 of the BMPR1A protein (p.Tyr176Phe). The tyrosine residue is highly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. |
| Ambry Genetics | RCV003339596 | SCV004059778 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-30 | criteria provided, single submitter | clinical testing | The p.Y176F variant (also known as c.527A>T), located in coding exon 5 of the BMPR1A gene, results from an A to T substitution at nucleotide position 527. The tyrosine at codon 176 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |