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Gene | ATM |
Variant | A2622V |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | ATM A2622V does not lie within any known functional domains of the Atm protein (UniProt.org). ATM A2622V does not demonstrate defects in protein stability, kinase activity, or radiation-induced nuclear foci formation in cultured cells when the splicing defect resulting from the corresponding DNA change is corrected (PMID: 17389389, PMID: 37438524), however, the corresponding DNA change (c.7865C>T) results in altered splicing of ATM leading to a deletion of 64 nucleotides (PMID: 14695534, PMID: 37438524) and loss of Atm expression in patient cells (PMID: 10330348), and therefore, is predicted to lead to a loss of Atm protein function. |
Associated Drug Resistance | |
Category Variants Paths |
ATM mutant ATM inact mut ATM A2622V |
Transcript | NM_000051.4 |
gDNA | chr11:g.108332838C>T |
cDNA | c.7865C>T |
Protein | p.A2622V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001351834.2 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
XM_006718843.5 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
XM_017017790.3 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
XM_047426975.1 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
XM_011542840.4 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
NM_000051.4 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
XM_011542843.3 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
XM_005271562.6 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
XM_047426976.1 | chr11:g.108332838C>T | c.7865C>T | p.A2622V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ATM A2622V | prostate cancer | sensitive | Olaparib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM A2622V, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). | detail... detail... 32343890 |