Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025387 | SCV001187567 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-04 | criteria provided, single submitter | clinical testing | The p.S218N variant (also known as c.653G>A), located in coding exon 6 of the BMPR1A gene, results from a G to A substitution at nucleotide position 653. The serine at codon 218 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
Invitae | RCV001359375 | SCV001555240 | uncertain significance | Juvenile polyposis syndrome | 2021-03-14 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). This variant has not been reported in the literature in individuals with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 826471). This variant is present in population databases (rs752893921, ExAC 0.002%). This sequence change replaces serine with asparagine at codon 218 of the BMPR1A protein (p.Ser218Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. |