Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000215774 | SCV000279787 | pathogenic | not provided | 2017-05-10 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in CHEK2 is denoted c.876delT at the cDNA level and p.Phe292LeufsX12 (F292LfsX12) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTTTTT[delT]GATG. The deletion causes a frameshift, which changes a Phenylalanine to a Leucine at codon 292, and creates a premature stop codon at position 12 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 pathogenic. |
Invitae | RCV000462314 | SCV000550473 | pathogenic | Familial cancer of breast | 2023-02-23 | 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: 234765). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This sequence change creates a premature translational stop signal (p.Phe292Leufs*12) 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). 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. |
Ambry Genetics | RCV000568161 | SCV000669266 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-23 | criteria provided, single submitter | clinical testing | The c.876delT pathogenic mutation, located in coding exon 7 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 876, causing a translational frameshift with a predicted alternate stop codon (p.F292Lfs*12). 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, |
RCV000568161 | SCV001735525 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-23 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 8 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. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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, |
RCV000462314 | SCV004045013 | pathogenic | Familial cancer of breast | 2023-06-27 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |