Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000685881 | SCV000813381 | uncertain significance | Familial cancer of breast | 2023-08-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 566140). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 67 of the CHEK2 protein (p.Ser67Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Color Diagnostics, |
RCV001191643 | SCV001359536 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-14 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 67 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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. |