Gene Variant Detail

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Gene ATM
Variant R2506_N2543del
Impact List deletion
Protein Effect loss of function
Gene Variant Descriptions ATM R2506_N2543del results in the deletion of 38 amino acids in the FAT domain of the Atm protein from amino acids 2506 to 2543 (UniProt.org). R2506_N2543del results in a loss of Atm protein expression and failure to induce expression of TP53 target genes upon DNA damage in patient-derived cells in culture (PMID: 23585524).
Associated Drug Resistance

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Transcript NM_000051.3
gDNA chr11:g.108331444_108331557del114
cDNA c.7516_7629del114
Protein p.R2506_N2543del
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001351834.1 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_017017790.2 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_005271562 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_017017789 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_006718843.4 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_005271562.5 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_011542840 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_011542840.3 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_005271561 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_017017790 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_006718843 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
NM_000051 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_011542843 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_011542843.2 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
NM_000051.3 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38
XM_017017789.2 chr11:g.108331444_108331557del114 c.7516_7629del114 p.R2506_N2543del RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ATM inact mut Advanced Solid Tumor predicted - sensitive Radiotherapy Clinical Study Actionable In a clinical study, treatment with radiotherapy resulted in greater therapeutic efficacy in advanced solid tumor patients harboring an ATM inactivating mutation (n=177) compared to those who harbored an ATM variant of unknown significance (n=180), demonstrating a significantly decreased 2-year cumulative incidence of irradiated progression, 13.2% versus 27.5% (p=0.001), respectively, and the greatest clinical benefit was observed in tumors with bi-allelic ATM inactivating mutations (PMID: 32726432). 32726432
ATM inact mut mantle cell lymphoma sensitive Bendamustine + Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) sensitized a mantle cell lymphoma cell line harboring an ATM inactivating mutation to Treanda (bendamustine) in cell culture, resulting in growth inhibition (PMID: 20739657). 20739657
ATM inact mut Advanced Solid Tumor sensitive E7449 Preclinical Actionable In a preclinical study, E7449 inhibited proliferation of a ATM-deficient cell line in culture, which demonstrated increased sensitivity compared to cells without DNA repair pathway mutations (PMID: 26513298). 26513298
ATM inact mut Advanced Solid Tumor predicted - sensitive BAY1895344 Phase I Actionable In a Phase I trial, BAY1895344 treatment was tolerated and resulted in an objective response rate of 36.4% (4/11, all partial responses) and a disease control rate of 63.6% (7/11) in patients with advanced solid tumors harboring ATM inactivating mutations and/or ATM protein expression loss (PMID: 32988960; NCT03188965). 32988960
ATM inact mut mantle cell lymphoma sensitive Olaparib + Valproic acid Preclinical - Cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib) and valproic acid worked synergistically to inhibit growth of a mantle cell lymphoma cell line harboring an ATM inactivating mutation in culture (PMID: 20739657). 20739657
ATM inact mut lymphoid leukemia sensitive Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, lymphoblastoid cell lines with ATM inactivation derived from ataxia-telangiectasia patients demonstrated increased sensitivity to Lynparza (olaparib) in culture, compared to ATM wild-type cell lines (PMID: 20739657). 20739657
ATM inact mut Advanced Solid Tumor sensitive Veliparib Preclinical - Cell culture Actionable In a preclinical study, an ATM-deficient cell line demonstrated increased sensitivity to Veliparib (ABT-888) compared to an ATM-reconstituted cell line, in culture (PMID: 21300883). 21300883
ATM inact mut mantle cell lymphoma sensitive Fludarabine + Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) sensitized a mantle cell lymphoma cell line harboring an ATM inactivating mutation to Fludara (fludarabine) in cell culture, resulting in decreased cell survival (PMID: 20739657). 20739657
ATM inact mut mantle cell lymphoma sensitive Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, a mantle cell lymphoma cell line with ATM inactivation demonstrated sensitivity to Lynparza (olaparib) in culture and in xenograft models (PMID: 20739657). 20739657
ATM inact mut chronic lymphocytic leukemia sensitive Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived chronic lymphocytic leukemia cells with inactivating mutations in ATM, that had been induced to proliferate in culture, demonstrated increased sensitivity to growth inhibition by Lynparza (olaparib) compared to ATM wild-type cells (PMID: 20739657). 20739657
ATM inact mut prostate cancer no benefit Rucaparib Phase II Actionable In a Phase II trial (TRITON2), activity of Rubraca (rucaparib) was limited in the cohort of patients with metastatic castrate-resistant prostate cancer harboring an ATM mutation presumed to be inactivating, with a radiographic response rate of 10.5% (2/19, including 1 patient with co-occurring CHEK2 alteration) and PSA response rate of 4.1% (2/49), and no radiographic responses in 11 patients with biallelic alterations in ATM or 11 patients with germline ATM alterations (PMID: 32086346; NCT02952534). 32086346
ATM inact mut prostate cancer sensitive Olaparib Phase II Actionable In a Phase II (TOPARP-B) trial, Lynparza (olaparib) treatment resulted in a composite overall response rate of 36.8% (7/19) and a RECIST objective response rate of 8.3% (1/12) in patients with castration-resistant prostate cancer harboring deleterious ATM mutations (PMID: 31806540; NCT01682772). 31806540
ATM inact mut prostate cancer sensitive Olaparib Guideline Actionable Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in ATM (NCCN.org). detail...
ATM inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment improved progression-free survival (7.4 vs 3.6 mo, HR=0.34, p<0.001), objective response rate (33%, 28/84 vs 2%, 1/43, OR=20.86, p<0.001), and median time to pain progression (HR=0.44, p=0.02) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in BRCA1/2 or ATM who progressed on hormone therapy (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM inact mut prostate cancer sensitive Olaparib Phase II Actionable In a Phase II clinical trial, 80% (4/5) of metastatic, castration-resistant prostate cancer patients harboring an ATM inactivating mutation responded to Lynparza (olaparib) (PMID: 26510020). 26510020
ATM mutant prostate cancer sensitive Olaparib Phase II Actionable In a Phase II clinical trial, 80% (4/5) of metastatic castration-resistant prostate cancer patients with ATM truncation mutations demonstrated response to Lynparza (olaparib) treatment (Cancer Res August 1, 2015 75:CT322). detail...
ATM mutant mantle cell lymphoma predicted - sensitive Ibrutinib + Venetoclax Phase II Actionable In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391). 30455436
ATM mutant prostate cancer not applicable N/A Guideline Risk Factor Germline ATM mutations are associated with increased risk of developing prostate cancer (NCCN.org). detail...
ATM mutant breast cancer no benefit Olaparib Case Reports/Case Series Actionable In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment did not result in an objective response in 4 patients with metastatic breast cancer harboring only germline mutations in ATM (PMID: 33119476; NCT03344965). 33119476
Molecular Profile Protein Effect Treatment Approaches
ATM R2506_N2543del loss of function PARP Inhibitor (Pan)