Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000456188 | SCV000550495 | pathogenic | Familial cancer of breast | 2023-06-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 410036). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gln11Profs*66) 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). |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759773 | SCV000889332 | pathogenic | not provided | 2017-11-15 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001188944 | SCV001356129 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 2 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 identified in 1/246382 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222517 | SCV002500560 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2022-03-21 | criteria provided, single submitter | clinical testing | Variant summary: CHEK2 c.31dupC (p.Gln11ProfsX66) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 246382 control chromosomes (gnomAD). c.31dupC has been reported in the literature in at least one individual affected with Hereditary Breast And Ovarian Cancer Syndrome (Cybulski_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Myriad Genetics, |
RCV000456188 | SCV004044478 | pathogenic | Familial cancer of breast | 2023-06-22 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |