Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219411 | SCV000276310 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | The c.1337delA pathogenic mutation, located in coding exon 11 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 1337, causing a translational frameshift with a predicted alternate stop codon (p.N446Tfs*23). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Gene |
RCV000254757 | SCV000322535 | likely pathogenic | not provided | 2016-02-01 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in CHEK2 is denoted c.1337delA at the cDNA level and p.Asn446ThrfsX23 (N446TfsX23) at the protein level. The normal sequence, with the base that is deleted in braces, is TACA[A]CTTC. The deletion causes a frameshift, which changes an Asparagine to a Threonine at codon 446, and creates a premature stop codon at position 23 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000254757 | SCV000601152 | likely pathogenic | not provided | 2017-07-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000547049 | SCV000633125 | pathogenic | Familial cancer of breast | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn446Thrfs*23) 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). 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: 232235). For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV000219411 | SCV000909475 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 12 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 a pancreatic neuroendocrine tumor (PMID: 30687805). This variant has not been identified 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. |
| Myriad Genetics, |
RCV000547049 | SCV004044938 | pathogenic | Familial cancer of breast | 2023-06-28 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV000547049 | SCV004217741 | pathogenic | Familial cancer of breast | 2022-05-16 | criteria provided, single submitter | clinical testing |