Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000205660 | SCV000259654 | uncertain significance | Familial cancer of breast | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 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 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: 219655). 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. 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. |
Counsyl | RCV000205660 | SCV000785925 | uncertain significance | Familial cancer of breast | 2018-01-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001582708 | SCV001819228 | uncertain significance | not provided | 2022-06-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports a deleterious effect on splicing |
Genetic Services Laboratory, |
RCV001818497 | SCV002070598 | uncertain significance | not specified | 2018-05-23 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000205660 | SCV004020132 | uncertain significance | Familial cancer of breast | 2023-03-08 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Color Diagnostics, |
RCV003584566 | SCV004361367 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-07 | criteria provided, single submitter | clinical testing | This variant causes a T to C nucleotide substitution at the +6 position of intron 8 of the CHEK2 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CHEK2-related cancers, but it has been reported in an unaffected individual (PMID: 28779002). 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. |