ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1475_1477del (p.Lys492del)

dbSNP: rs1555912075
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575472 SCV000661749 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing The c.1475_1477delAGA variant (also known as p.K492DEL) is located in coding exon 13 of the CHEK2 gene. This variant results from an in-frame AGA deletion between nucleotide positions 1475 and 1477. This results in the deletion of a lysine residue at codon 492. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 3626 samples (7252 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 200000 alleles tested) in our clinical cohort. This nucleotide region is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000575472 SCV001354403 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-04 criteria provided, single submitter clinical testing This variant causes an in-frame deletion of one amino acid in exon 14 of the CHEK2 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. 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). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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