Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000461120 | SCV000550487 | uncertain significance | Familial cancer of breast | 2023-03-15 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 410032). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 487 of the CHEK2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CHEK2 protein. This variant also falls at the last nucleotide of exon 13, which is part of the consensus splice site for this exon. |
| Ambry Genetics | RCV002393135 | SCV002696991 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-08 | criteria provided, single submitter | clinical testing | The c.1461G>A variant (also known as p.Q487Q) is located in coding exon 12 of the CHEK2 gene. This variant results from a G to A substitution at nucleotide position 1461. This nucleotide substitution does not change the glutamine at codon 487. However, this change occurs in the last base pair of coding exon 12, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV000461120 | SCV005058418 | uncertain significance | Familial cancer of breast | 2023-11-28 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV004596196 | SCV005089750 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing |