ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1407G>A (p.Val469=)

gnomAD frequency: 0.00190  dbSNP: rs17881378
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212461 SCV000167692 benign not specified 2014-01-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000124265 SCV000213083 likely benign Hereditary cancer-predisposing syndrome 2014-06-24 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000200578 SCV000252811 benign Familial cancer of breast 2024-02-01 criteria provided, single submitter clinical testing
Counsyl RCV000200578 SCV000488583 likely benign Familial cancer of breast 2016-05-09 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000124265 SCV000684589 likely benign Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589618 SCV000698774 benign not provided 2016-03-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589618 SCV000888104 benign not provided 2022-11-08 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000212461 SCV002070842 benign not specified 2021-12-13 criteria provided, single submitter clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State RCV002225406 SCV002505154 benign Hereditary breast ovarian cancer syndrome 2022-04-19 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000124265 SCV002537370 benign Hereditary cancer-predisposing syndrome 2020-12-12 criteria provided, single submitter curation
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003149857 SCV003838781 likely benign Breast and/or ovarian cancer 2021-10-29 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000200578 SCV004017381 benign Familial cancer of breast 2023-07-07 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000200578 SCV004020182 benign Familial cancer of breast 2023-03-09 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000589618 SCV004563300 benign not provided 2023-06-19 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000589618 SCV001552585 likely benign not provided no assertion criteria provided clinical testing The CHEK2 p.Val469= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs17881378) as “With other allele” and ClinVar (classified as likely benign by Ambry Genetics, Counsyl, Quest Diagnostics, and Color; and as benign by GeneDx, Invitae, and Integrated Genetics). The variant was identified in control databases in 152 of 260148 chromosomes at a frequency of 0.0006, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 143 of 22576 chromosomes (freq: 0.006334), Latino in 7 of 34216 chromosomes (freq: 0.000205), and European (Non-Finnish) in 2 of 122014 chromosomes (freq: 0.000016), while the variant was not observed in the Other, Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.Val469= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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