ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.673dup (p.Thr225fs)

dbSNP: rs1342011335
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476282 SCV000550423 pathogenic Familial cancer of breast 2023-05-30 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: 409998). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr225Asnfs*20) 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).
Ambry Genetics RCV002365646 SCV002666967 pathogenic Hereditary cancer-predisposing syndrome 2021-08-11 criteria provided, single submitter clinical testing The c.673dupA variant, located in coding exon 4 of the CHEK2 gene, results from a duplication of A at nucleotide position 673, causing a translational frameshift with a predicted alternate stop codon (p.T225Nfs*20). 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.
Myriad Genetics, Inc. RCV000476282 SCV004043425 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.
Color Diagnostics, LLC DBA Color Health RCV002365646 SCV004361387 pathogenic Hereditary cancer-predisposing syndrome 2021-07-29 criteria provided, single submitter clinical testing This variant inserts 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. 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.

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