Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000565297 | SCV000673256 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-03-10 | criteria provided, single submitter | clinical testing | The p.K177* pathogenic mutation (also known as c.529A>T), located in coding exon 3 of the CHEK2 gene, results from an A to T substitution at nucleotide position 529. This changes the amino acid from a lysine to a stop codon within coding exon 3. 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. |
Invitae | RCV000700074 | SCV000828814 | pathogenic | Familial cancer of breast | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys177*) 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 present in population databases (rs796389290, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 22527104). This variant is also known as c.658T>A (p.K220*). ClinVar contains an entry for this variant (Variation ID: 485522). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Color Diagnostics, |
RCV000565297 | SCV001343629 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 4 of the CHEK2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/251420 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. |
Myriad Genetics, |
RCV000700074 | SCV004045231 | pathogenic | Familial cancer of breast | 2023-06-26 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |