Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482348 | SCV000566438 | uncertain significance | not provided | 2015-05-04 | criteria provided, single submitter | clinical testing | This variant is denoted CHEK2 c.1461+5G>T or IVS13+5G>T and consists of a G>T nucleotide substitution at the +5 position of intron 13 of the CHEK2 gene. Multiple in silico models predict this variant to damage the nearby natural donor site, and to possibly cause abnormal gene splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. The guanine (G) nucleotide that is altered is conserved across species. Based on currently available information, it is unclear whether CHEK2 c.1461+5G>T is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Invitae | RCV000802634 | SCV000942475 | uncertain significance | Familial cancer of breast | 2023-06-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 13 of the CHEK2 gene. It does not directly change the encoded amino acid sequence of the CHEK2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 418975). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. |
Ambry Genetics | RCV002395146 | SCV002696984 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-26 | criteria provided, single submitter | clinical testing | The c.1461+5G>T intronic variant results from a G to T substitution 5 nucleotides after coding exon 12 in the CHEK2 gene. 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. |
Center for Genomic Medicine, |
RCV002465683 | SCV002761096 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |