ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1593G>A (p.Glu531=)

gnomAD frequency: 0.00001  dbSNP: rs758555487
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214895 SCV000274477 likely benign Hereditary cancer-predisposing syndrome 2015-03-04 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.
GeneDx RCV001711509 SCV000520922 likely benign not provided 2020-01-28 criteria provided, single submitter clinical testing
Invitae RCV000465325 SCV000560998 benign Familial cancer of breast 2024-01-29 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000214895 SCV000684614 likely benign Hereditary cancer-predisposing syndrome 2016-09-16 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001147093 SCV001307871 uncertain significance CHEK2-Related Cancer Susceptibility 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000440523 SCV001448547 likely benign not specified 2020-11-19 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000440523 SCV004024322 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000465325 SCV001553085 likely benign Familial cancer of breast no assertion criteria provided clinical testing The CHEK2 p.Glu531= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs758555487) as "With Likely benign allele ", and in ClinVar (classified as benign by Invitae; as likely benign by Ambry Genetics, GeneDx and Color). The variant was identified in control databases in 54 of 260100 chromosomes at a frequency of 0.0002 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 1 of 22578 chromosomes (freq: 0.00004), Other in 1 of 6276 chromosomes (freq: 0.000159), European in 1 of 121982 chromosomes (freq: 0.000008), and South Asian in 51 of 30512 chromosomes (freq: 0.002), while the variant was not observed in the Latino, Ashkenazi Jewish, East Asian, and Finnish, populations. The p.Glu531= 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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