ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1259+8A>G (rs368388249)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506517 SCV000601146 uncertain significance not specified 2016-11-04 criteria provided, single submitter clinical testing
Invitae RCV000527244 SCV000633115 uncertain significance Familial cancer of breast 2018-11-15 criteria provided, single submitter clinical testing This sequence change falls in intron 11 of the CHEK2 gene. It does not directly change the encoded amino acid sequence of the CHEK2 protein. This variant is present in population databases (rs368388249, ExAC 0.006%). This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 439090). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000581749 SCV000689643 likely benign Hereditary cancer-predisposing syndrome 2017-03-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589519 SCV000698765 uncertain significance not provided 2016-02-23 criteria provided, single submitter clinical testing Variant summary: The c.1259+8A>G in CHEK2 gene is an intronic change that alters a no-nconserved nucleotide. 2/5 in silico tools via Alamut predict this variant to have some effect on splicing pattern, however, these predictions have yet to be confirmed by in vitro/in vivo functional studies. The variant has not, to our knowledge, been reported in the affected individuals, nor has it been cited by reputable clinical laboratories/diagnostic centers. The variant is present in ExAC at low frequency (0.064%), exclusively in European cohort; this frequency does not exceed the maximum frequency for a pathogenic variant in CHEK2 gene (0.03%). The variant may be an ethnic specific rare polymorphism, however, additional information is needed to evaluate this variant with confidence. Taken together, the variant was classified as VUS until new information becomes available.

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