ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.622del (p.Asp208fs)

gnomAD frequency: 0.00001  dbSNP: rs773955899
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Total submissions: 4
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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, LLC DBA Color Health 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, Inc. 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.

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