Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000568969 | SCV000669238 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-05-31 | criteria provided, single submitter | clinical testing | The c.622delG pathogenic mutation, located in coding exon 4 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 622, causing a translational frameshift with a predicted alternate stop codon (p.D208Ifs*9). This alteration was reported in a BRCA1/2-negative breast cancer patient (Fan Z et al. Breast Cancer Res. Treat., 2018 May;169:59-67). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Color Diagnostics, |
RCV000568969 | SCV002052901 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-03-02 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 5 of the CHEK2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with breast cancer (PMID: 29356917). This variant has been identified in 2/229194 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of CHEK2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Invitae | RCV001858287 | SCV002121390 | pathogenic | Familial cancer of breast | 2020-12-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp208Ilefs*9) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with breast cancer (PMID: 28724667). ClinVar contains an entry for this variant (Variation ID: 483360). This variant is present in population databases (rs773955899, ExAC 0.04%). |
Myriad Genetics, |
RCV001858287 | SCV004042936 | pathogenic | Familial cancer of breast | 2023-06-26 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |