Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129580 | SCV000184362 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-30 | criteria provided, single submitter | clinical testing | The c.444+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 2 in the CHEK2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000206661 | SCV000259262 | uncertain significance | Familial cancer of breast | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 3 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 (rs189961251, gnomAD 0.007%). 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: 141186). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis provides insufficient evidence to determine the effect of this variant on CHEK2 splicing (Invitae). 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. |
Baylor Genetics | RCV000206661 | SCV004217746 | uncertain significance | Familial cancer of breast | 2022-02-21 | criteria provided, single submitter | clinical testing |