Annotation Detail

Information
Associated Genes
ATM
Associated Variants
ATM p.Ser2289Ter (p.S2289*) ( ENST00000713844.1, ENST00000675843.1, ENST00000452508.7, ENST00000278616.10, ENST00000525729.5, ENST00000601453.3 )
ATM p.Ser2289Ter (p.S2289*) ( ENST00000278616.10, ENST00000452508.7, ENST00000601453.3, ENST00000675843.1, ENST00000713844.1, ENST00000525729.5 )
Associated Disease
prostate cancer
Source Database
CIViC Evidence
Description
Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. Overall, 4/6 patients (3/5 with no other identified aberrations in DNA repair genes) with several germline and somatic aberrations of ATM had a response. Responders included a single patient with a somatic frameshift mutation (ATM V2288fs*1) predicted to result in truncation prior to the PI3K catalytic domain and other domains for p53 recognition and response to DNA damage. No other alterations in ATM were observed; however, this patient also had frameshift mutations in MLH3, MRE11 and NBN.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/647
Gene URL
https://civic.genome.wustl.edu/links/genes/69
Variant URL
https://civic.genome.wustl.edu/links/variants/243
Rating
3
Evidence Type
Predictive
Disease
Prostate Cancer
Evidence Direction
Supports
Drug
Olaparib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26510020
Drugs
Drug NameSensitivitySupported
OlaparibSensitivitytrue