Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000217734 | SCV000277552 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-14 | criteria provided, single submitter | clinical testing | The c.848C>A (p.P283H) alteration is located in exon 8 (coding exon 7) of the CHEK2 gene. This alteration results from a C to A substitution at nucleotide position 848, causing the proline (P) at amino acid position 283 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000692317 | SCV000820132 | uncertain significance | Familial cancer of breast | 2023-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 283 of the CHEK2 protein (p.Pro283His). 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. ClinVar contains an entry for this variant (Variation ID: 233219). 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, |
RCV000217734 | SCV001351705 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-12 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with histidine at codon 283 of the CHEK2 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant 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). 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. |