Annotation Detail

Information
Associated Genes
KRAS
Associated Variants
KRAS p.Ala146Val (p.A146V) ( ENST00000311936.8, ENST00000557334.6, ENST00000256078.10, ENST00000685328.1, ENST00000688940.1, ENST00000692768.1, ENST00000693229.1 )
KRAS p.Ala146Val (p.A146V) ( ENST00000256078.10, ENST00000311936.8, ENST00000557334.6, ENST00000685328.1, ENST00000688940.1, ENST00000692768.1, ENST00000693229.1 )
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
Case report of a patient with metastatic lung adenocarcinoma. Whole exome sequencing of the metastatic tumor revealed KRAS A146V, STK11 frameshift deletion and ATM alteration. Preclinical evidence led to administration of CDK4 inhibitor LY2835219. Specifically, the PHIAL algorithm nominated this variant as actionable on the basis of a predicted synthetic lethal relationship between activated KRAS and CDK4. The patient achieved stable disease and was on treatment for 16 weeks which was the patients best and only clinical response to any cancer-directed therapy.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/794
Gene URL
https://civic.genome.wustl.edu/links/genes/30
Variant URL
https://civic.genome.wustl.edu/links/variants/322
Rating
2
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Abemaciclib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
24836576
Drugs
Drug NameSensitivitySupported
AbemaciclibSensitivitytrue