Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000700391 | SCV000829143 | uncertain significance | Familial cancer of breast | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 90 of the CHEK2 protein (p.Pro90Ser). This variant is present in population databases (rs777588170, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 577593). 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. |
| Ambry Genetics | RCV001016305 | SCV001177248 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-20 | criteria provided, single submitter | clinical testing | The p.P90S variant (also known as c.268C>T), located in coding exon 1 of the CHEK2 gene, results from a C to T substitution at nucleotide position 268. The proline at codon 90 is replaced by serine, an amino acid with similar properties. This alteration has been reported with a carrier frequency of 0.00014 in 7051 unselected breast cancer patients and 0.00009 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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. |
| Gene |
RCV002473119 | SCV002770382 | uncertain significance | not provided | 2023-08-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in individuals with breast and biliary tract cancers, and also in unaffected controls (Momozawa et al., 2018; Okawa et al., 2023); This variant is associated with the following publications: (PMID: 36243179, 30287823) |