ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.952del (p.Arg318fs)

dbSNP: rs749153163
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000706341 SCV000835384 pathogenic Familial cancer of breast 2021-07-07 criteria provided, single submitter clinical testing This variant is present in population databases (rs749153163, ExAC 0.001%). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). This variant has been observed in individual(s) with breast cancer (PMID: 31360903). ClinVar contains an entry for this variant (Variation ID: 582301). This sequence change creates a premature translational stop signal (p.Arg318Alafs*2) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798966 SCV002043415 likely pathogenic Breast and/or ovarian cancer 2020-01-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002369968 SCV002688276 pathogenic Hereditary cancer-predisposing syndrome 2021-07-06 criteria provided, single submitter clinical testing The c.952delC pathogenic mutation, located in coding exon 8 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 952, causing a translational frameshift with a predicted alternate stop codon (p.R318Afs*2). 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. RCV000706341 SCV004045143 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478448 SCV004221759 pathogenic not provided 2023-07-19 criteria provided, single submitter clinical testing The CHEK2 c.952del (p.Arg318Alafs*2) variant alters the translational reading frame of the CHEK2 mRNA and causes the premature termination of CHEK2 protein synthesis. This variant has been reported in the published literature in an individual with breast cancer (PMID: 31360903 (2019)). The frequency of this variant in the general population, 0.0000088 (1/113758 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.

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