ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.847-10C>G (rs745745105)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233752 SCV000289709 benign Familial cancer of breast 2017-10-27 criteria provided, single submitter clinical testing
Counsyl RCV000233752 SCV000489630 likely benign Familial cancer of breast 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000442363 SCV000512590 benign not specified 2015-07-21 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.
Color RCV000580112 SCV000684687 benign Hereditary cancer-predisposing syndrome 2017-05-29 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000442363 SCV000806889 benign not specified 2017-05-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000442363 SCV000917238 benign not specified 2018-06-22 criteria provided, single submitter clinical testing Variant summary: CHEK2 c.847-10C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 6-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in CHEK2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00031), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. The variant, c.847-10C>G, was reported in the literature, however, with limited information (Young_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as benign.

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