ClinVar Miner

Submissions for variant NM_004985.5(KRAS):c.451-5538A>G

gnomAD frequency: 0.00001  dbSNP: rs755967833
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780368 SCV000917566 uncertain significance not specified 2017-10-10 criteria provided, single submitter clinical testing Variant summary: The KRAS c.562A>G (p.Ile188Val) variant located in the small GTP-binding protein domain (via InterPro) involves the alteration of a non-conserved nucleotide and 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant was found in 3/276902 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000083 (2/24028). This frequency is about 7 times the estimated maximal expected allele frequency of a pathogenic KRAS variant (0.0000125), suggesting this is possibly a benign polymorphism found primarily in the populations of African origin, although the allele count is small. In addition, this observation needs to be cautiously considered due to the gnomAD cohort could harbor individuals with a KRAS phenotype. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
PreventionGenetics, part of Exact Sciences RCV004549859 SCV004115455 uncertain significance KRAS-related disorder 2023-06-05 criteria provided, single submitter clinical testing The KRAS c.562A>G variant is predicted to result in the amino acid substitution p.Ile188Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-25368383-T-C). Of note, in a different transcript (NM_004985), this variant is deep intronic (c.451-5538A>G). In ClinVar, this variant is interpreted as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/632869/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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