ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.14_20del (p.Ser5fs)

dbSNP: rs757016287
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220544 SCV000277759 pathogenic Hereditary cancer-predisposing syndrome 2023-03-08 criteria provided, single submitter clinical testing The c.14_20delCGGATGT pathogenic mutation, located in coding exon 1 of the CHEK2 gene, results from a deletion of 7 nucleotides at nucleotide positions 14 to 20, causing a translational frameshift with a predicted alternate stop codon (p.S5Lfs*54). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199925 SCV001370706 likely pathogenic Hereditary breast ovarian cancer syndrome 2020-05-07 criteria provided, single submitter clinical testing Variant summary: CHEK2 c.14_20delCGGATGT (p.Ser5LeufsX54) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 245902 control chromosomes. To our knowledge, no occurrence of c.14_20delCGGATGT in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneDx RCV001551330 SCV001771812 likely pathogenic not provided 2019-05-20 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016)
Invitae RCV001854693 SCV002245897 pathogenic Familial cancer of breast 2022-11-23 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs757016287, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Ser5Leufs*54) 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). ClinVar contains an entry for this variant (Variation ID: 233394). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV001854693 SCV004044449 pathogenic Familial cancer of breast 2023-06-22 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV001854693 SCV004217752 likely pathogenic Familial cancer of breast 2021-10-19 criteria provided, single submitter clinical testing

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