Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001241110 | SCV001414105 | uncertain significance | Familial cancer of breast | 2019-10-29 | 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 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 C15"). This variant has not been reported in the literature in individuals with CHEK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with tyrosine at codon 208 of the CHEK2 protein (p.Asp208Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. |
Ambry Genetics | RCV002366064 | SCV002658499 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | The p.D208Y variant (also known as c.622G>T), located in coding exon 4 of the CHEK2 gene, results from a G to T substitution at nucleotide position 622. The aspartic acid at codon 208 is replaced by tyrosine, an amino acid with highly dissimilar 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. |