Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479812 | SCV000570299 | uncertain significance | not provided | 2016-05-13 | criteria provided, single submitter | clinical testing | This in-frame deletion of 3 nucleotides in CHEK2 is denoted c.486_488delTCA at the cDNA level and p.His163del (H163del) at the protein level. The normal sequence, with the bases that are deleted in braces, is AAGA[TCA]CAGT. This deletion of a single Histidine residue occurs at a position that is conserved in mammals and is located in the FHA domain (Desrichard 2011, Roeb 2012, UniProt). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider CHEK2 His163del to be a variant of uncertain significance. |
| Invitae | RCV001320639 | SCV001511434 | uncertain significance | Familial cancer of breast | 2021-10-07 | criteria provided, single submitter | clinical testing | This variant, c.486_488del, results in the deletion of 1 amino acid(s) of the CHEK2 protein (p.His163del), but otherwise preserves the integrity of the reading frame. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 421182). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (ExAC no frequency). |