About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.2522A>C, p.(Asp841Ala)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen ATM VCEP v1.5.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS1Strong
BS1 · strong
ATM VCEP BS1_Strong is met: grpmax filtering allele frequency in gnomAD v4.1 is 0.1156%, exceeding the >0.05% threshold. The variant is present in 127 alleles including 3 homozygotes in v4.1, and 43 alleles including 1 homozygote in v2.1, with highest frequency in the South Asian population (v4.1 AF=0.135%). This population frequency is incompatible with a highly penetrant pathogenic ATM variant.
BP4Supporting
BP4 · supporting
ATM VCEP BP4_Supporting for missense variants is met: REVEL score is 0.139, which is ≤0.249. Additionally, SpliceAI predicts no splice impact (max delta = 0.00, ≤0.1), and BayesDel score is -0.415893 (benign range). Multiple computational lines of evidence suggest no deleterious effect.
Recorded classification: Likely benign
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule18 (1 Benign.Strong + 1 Benign.Supporting) with applied criteria: BS1 strong, BP4 supporting; maps to Likely Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
127 / 1,614,172 alleles
gnomAD v4.1: 127 / 1,614,172 alleles. Recorded AF 7.86781e-05. Recorded homozygote count 3.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000171039; MAF= 0.01710%, 43/251404 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00137201; MAF= 0.13720%, 42/30612 alleles, homozygotes = 1); grpmax FAF= 0.00104332.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
12 reported laboratory submissions
7 Likely benign · 5 Uncertain significance.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ATM, a kinase involved in the DNA damage response, is mutated in various solid and hematologic malignancies.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen ATM VCEP v1.5.0, with the data and sources behind each one.
27 criteria with recorded statuses: 2 met · 7 not met · 2 not assessed · 16 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The variant NM_000051.4:c.2522A>C (p.Asp841Ala) is present in gnomAD v4.1 at a grpmax filtering allele frequency of 0.1156% (127 alleles, including 3 homozygotes), exceeding the ATM VCEP BS1_Strong threshold of >0.05%. This population frequency is incompatible with a highly penetrant pathogenic ATM variant.
Computational predictors are consistent with a benign effect: REVEL score is 0.139 (below the BP4_Supporting threshold of ≤0.249), SpliceAI predicts no splice impact (max delta = 0.00), and BayesDel score is -0.415893 (benign range).
The VCEP ATM functional scoring table (Suppl_TableS1, PMID 40580951) classifies D841A as 'Functional' with high confidence, placing it in the non-damaging category among ATM missense variants.
No variant-specific functional evidence supporting pathogenicity was identified in the literature; six full-text papers were reviewed and none mention this variant.
No criteria match.
Met · 2
BS1 StrongATM VCEP BS1_Strong is met: grpmax filtering allele frequency in gnomAD v4.1 is 0.1156%, exceeding the >0.05% threshold. The variant is present in 127 alleles including 3 homozygotes in v4.1, and 43 alleles including 1 homozygote in v2.1, with highest frequency in the South Asian population (v4.1 AF=0.135%). This population frequency is incompatible with a highly penetrant pathogenic ATM variant. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 0.1156% (> 0.05% VCEP BS1_Strong threshold)
- 3 homozygotes in v4.1
- 1 homozygote in v2.1
- highest sub-population AF = 0.135% in South Asian.
Sources
BP4 SupportingATM VCEP BP4_Supporting for missense variants is met: REVEL score is 0.139, which is ≤0.249. Additionally, SpliceAI predicts no splice impact (max delta = 0.00, ≤0.1), and BayesDel score is -0.415893 (benign range). Multiple computational lines of evidence suggest no deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL = 0.139 (≤ 0.249 threshold)
- SpliceAI max delta = 0.00
- BayesDel = -0.415893 (benign)
- AlphaMissense = 0.1004 (benign).
Sources
Not met · 7 · evaluated, threshold not reached
PS1 PS1 requires a previously established pathogenic missense change at the same residue. All alternative substitutions at Asp841 (D841V, D841G, D841Y, D841N, D841H, D841E) are classified as Uncertain significance or Conflicting classifications in ClinVar and as 'Functional' (not pathogenic) in the VCEP functional scoring table (Suppl_TableS1). No pathogenic comparator exists at this residue. Details ▾Hide ▴
Evidence considered
- ClinVar lists all D841 missense variants as VUS or conflicting
- VCEP Suppl_TableS1 classifies D841A as 'Functional' with REVEL 0.139 and no pathogenic designation.
Sources
clinvar ↗vcep_suppl_tables1_pmid_40580951
PS3 No variant-specific functional studies were identified for NM_000051.4:c.2522A>C (p.Asp841Ala) in the literature reviewed. The VCEP functional spreadsheet (Suppl_TableS1) classifies D841A as 'Functional' based on in silico prediction, not experimental functional assay data. No published functional assay includes this specific variant. Details ▾Hide ▴
Evidence considered
- VCEP Suppl_TableS1 lists D841A with combined_score 0.17 and classification 'Functional' based on computational prediction only
- no variant-specific experimental functional data found in any paper.
Still missing
- No experimental functional studies (kinase assay
- radiosensitivity assay) include c.2522A>C.
Sources
vcep_suppl_tables1_pmid_40580951
PS4 PS4 requires case-control studies demonstrating significant enrichment in affected individuals. No case-control study or proband enrichment analysis was identified for this variant. The variant is observed at appreciable population frequency (gnomAD v4.1 AF=0.00787%, 127 alleles, 3 homozygotes), inconsistent with a highly penetrant pathogenic variant enriched in cases. Details ▾Hide ▴
Evidence considered
- No case-control studies found
- gnomAD v4.1 shows 127 alleles and 3 homozygotes.
Sources
PM2 ATM VCEP PM2_Supporting requires allele frequency ≤0.001% in gnomAD v4. This variant has AF=0.00787% (127/1,614,172 alleles) in gnomAD v4.1, exceeding the PM2 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 0.00787% (127 alleles) exceeds VCEP PM2_Supporting threshold of ≤0.001%.
Sources
PP3 ATM VCEP PP3_Supporting for missense variants requires REVEL score >0.7333. The REVEL score for c.2522A>C (p.Asp841Ala) is 0.139, well below the threshold. SpliceAI max delta score is 0.00, also not meeting the splicing prediction threshold (≥0.2). Details ▾Hide ▴
Evidence considered
- REVEL = 0.139 (< 0.7333 threshold)
- SpliceAI max delta = 0.00
- BayesDel = -0.415893 (benign).
Sources
BA1 ATM VCEP BA1 requires grpmax filtering allele frequency >0.5% in gnomAD v4. The grpmax FAF for this variant is 0.1156%, which is below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 0.1156% (< 0.5% BA1 threshold).
Sources
BS3 No variant-specific benign functional evidence was identified. The VCEP functional spreadsheet classifies D841A as 'Functional' based on computational prediction, not experimental assay data. No published experimental study (ATM kinase assay, radiosensitivity assay) includes c.2522A>C. Details ▾Hide ▴
Evidence considered
- VCEP Suppl_TableS1 classification: 'Functional' (computational
- not experimental)
- no experimental functional rescue data available.
Still missing
- No experimental benign functional evidence (kinase rescue
- radiosensitivity rescue) for this variant.
Sources
vcep_suppl_tables1_pmid_40580951
Not assessed · 2 · no assessment recorded
PP1 No segregation data are available for this variant. ATM VCEP PP1 applies to autosomal recessive (A-T) conditions with affected relatives; no proband or family segregation information was identified. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- Segregation data unavailable.
BP2 BP2 requires proband data evaluated through the ATM PM3/BP2 point table. No proband-level data (A-T affected or unaffected individuals with phased genotypes) were available for this variant. The 3 homozygotes in gnomAD v4.1 suggest potential BP2 applicability but formal assessment requires individual-level phenotype confirmation and use of the VCEP PM3/BP2 scoring table. Details ▾Hide ▴
Evidence considered
- 3 homozygotes observed in gnomAD v4.1
- but no individual-level phenotype or phase data available for formal BP2 scoring.
Still missing
- No proband-level phenotype and phase data for PM3/BP2 table scoring.
Sources
gnomad_v4 ↗vcep_atm_pm3_bp2_1_5
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is restricted to null variants (nonsense, frameshift, canonical splice sites); NM_000051.4:c.2522A>C is a missense variant (p.Asp841Ala) and does not qualify for PVS1 under the ATM VCEP PVS1 decision tree. Details ▾Hide ▴
Evidence considered
- Missense variant
- not a null variant per PVS1 definition.
Sources
vcep_atm_pvs1_1_5
PS2 VCEPPer ATM VCEP v1.5.0, PS2 is not applicable for ATM: informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PM1 VCEPPer ATM VCEP v1.5.0, PM1 is not applicable: benign and pathogenic variants occur within the same domains and germline mutational hotspots are not well defined at this time. Details ▾Hide ▴
PM5 N/AATM VCEP PM5_Supporting is restricted to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, or splice variants with PVS1_Strength(RNA). PM5 is explicitly not for use with missense changes per VCEP instructions. Details ▾Hide ▴
Evidence considered
- Missense variant
- VCEP PM5 rule applies only to truncating/splice variants
- not missense.
Sources
cspec ↗pm5_candidates
PM6 VCEPPer ATM VCEP v1.5.0, PM6 is not applicable for ATM: informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PP2 VCEPPer ATM VCEP v1.5.0, PP2 is not applicable: ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
PP4 VCEPPer ATM VCEP v1.5.0, PP4 is not applicable: breast cancer has multiple genetic etiologies (genetic heterogeneity) with no features that can readily distinguish hereditary from sporadic causes. For A-T, evidence is built into the PM3/BP2 table. Details ▾Hide ▴
PP5 VCEPPer ATM VCEP v1.5.0, PP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
- VCEP specification explicitly marks PP5 as not applicable for this VCEP.
Sources
BS2 VCEPPer ATM VCEP v1.5.0, BS2 is not applicable: ATM has incomplete penetrance. Details ▾Hide ▴
BS4 VCEPPer ATM VCEP v1.5.0, BS4 is not applicable: co-segregation analysis in low-penetrance genes can lead to false positive results, and informative lack of co-segregation in A-T families is too rare. Details ▾Hide ▴
BP1 VCEPPer ATM VCEP v1.5.0, BP1 is not applicable: missense pathogenic variants are known for ATM. Details ▾Hide ▴
BP3 VCEPSkipped: in-frame deletions/insertions in repetitive regions; not applicable to this substitution variant. Details ▾Hide ▴
Evidence considered
- Not an in-frame deletion/insertion.
BP5 VCEPPer ATM VCEP v1.5.0, BP5 is not applicable: cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and ATM has low penetrance. Details ▾Hide ▴
BP6 VCEPPer ATM VCEP v1.5.0, BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
- VCEP specification explicitly marks BP6 as not applicable for this VCEP.
Sources
BP7 N/ABP7 applies to synonymous and deep intronic variants. NM_000051.4:c.2522A>C is a missense variant (p.Asp841Ala) and does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 restricted to synonymous and deep intronic variants.
Sources
PS5 N/APS5 is not defined in the ATM VCEP v1.5.0 criteria set. Under generic ACMG/AMP, PS5 requires a reputable source to report the variant as pathogenic; ClinVar classifies this variant as Likely benign / Uncertain significance with no expert panel pathogenic assertion. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.2522A>C
- Protein (HGVS p.)
- NP_000042.3:p.(Asp841Ala)
- GRCh38
- chr11:108267226 A>C
- GRCh37
- chr11:108137953 A>C
- ClinVar
- 184552
Gene diagram
Every interpreted variant in ATM, mapped onto the exon structure of NM_000051.4. Select a row to find it on the plot.
ATMNM_000051.4
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in ATM
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
127 / 1,614,172 alleles
AF 7.87e-05 · 3 homozygotes · FAF 0.00116
gnomAD v2.1
43 / 251,404 alleles
AF 0.000171 · 1 homozygotes · FAF 0.00104
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7.9e-05 · 127 / 1,614,172 alleles · 3 hom · FAF 0.0012
| South Asian123 / 91,086 | 0.00143 hom |
| Remaining individuals4 / 62,506 | 6.4e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 0.00017 · 43 / 251,404 alleles · 1 hom · FAF 0.001
| South Asian42 / 30,612 | 0.00141 hom |
| Remaining individuals1 / 6,138 | 0.00016 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish).
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.86781e-05; MAF= 0.00787%, 127/1614172 alleles, homozygotes = 3) and has highest observed frequency in the South Asian population (AF= 0.00135037; MAF= 0.13504%, 123/91086 alleles, homozygotes = 3); grpmax FAF= 0.00115569.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000171039; MAF= 0.01710%, 43/251404 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00137201; MAF= 0.13720%, 42/30612 alleles, homozygotes = 1); grpmax FAF= 0.00104332.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.139
- BayesDel
- -0.416
How the predictions were used
BP4 SupportingATM VCEP BP4_Supporting for missense variants is met: REVEL score is 0.139, which is ≤0.249. Additionally, SpliceAI predicts no splice impact (max delta = 0.00, ≤0.1), and BayesDel score is -0.415893 (benign range). Multiple computational lines of evidence suggest no deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL = 0.139 (≤ 0.249 threshold)
- SpliceAI max delta = 0.00
- BayesDel = -0.415893 (benign)
- AlphaMissense = 0.1004 (benign).
Sources
PP3 ATM VCEP PP3_Supporting for missense variants requires REVEL score >0.7333. The REVEL score for c.2522A>C (p.Asp841Ala) is 0.139, well below the threshold. SpliceAI max delta score is 0.00, also not meeting the splicing prediction threshold (≥0.2). Details ▾Hide ▴
Evidence considered
- REVEL = 0.139 (< 0.7333 threshold)
- SpliceAI max delta = 0.00
- BayesDel = -0.415893 (benign).
Sources
BP7 N/ABP7 applies to synonymous and deep intronic variants. NM_000051.4:c.2522A>C is a missense variant (p.Asp841Ala) and does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 restricted to synonymous and deep intronic variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.139. BayesDel score = -0.415893.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.ACMG/AMP standards and guidelines for interpretation of sequence variants. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in this paper.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Describes a standardized DNA variant scoring system for Mendelian disorders. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in this paper.Does not name this variant
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PMID 26689913 ↗Patterns and functional implications of rare germline variants across 12 cancer types.Lu C et al. · 2015Systematic analysis of rare germline variants across 12 cancer types using TCGA data. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in this paper.Does not name this variant
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PMID 33552952 ↗Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening.Kadri MSN et al. · 2020Mutational landscape analysis of Indian hereditary breast and ovarian cancer cohort using amplicon sequencing of 144 cases. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in the full text.Does not name this variant
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PMID 34242744 ↗Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in this paper.Does not name this variant
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PMID 34326862 ↗Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach.Bhai P et al. · 2021Analysis of sequence and copy number variants in Canadian familial cancer cohort. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in the available abstract; only an image file (screenshot) was available.Does not name this variant
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PMID 17508274 ↗Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors.Berliner JL et al. · 2007NSGC recommendations for risk assessment and genetic counseling for hereditary breast and ovarian cancer. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in this paper.Does not name this variant
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PMID 24366402 ↗Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.USPSTF patient summary on genetic risk assessment for BRCA-related breast or ovarian cancer. NM_000051.4:c.2522A>C (p.Asp841Ala) was not identified in the available materials; only an image file (screenshot) was available.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
127 / 1,614,172 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
7 Likely benign · 5 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/639508985
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/184552/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108137953-A-C?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108267226-A-C?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108267226-A-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.2522…
- OncoKB ↗www.oncokb.org/gene/ATM/D841A
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.2522A%3EC
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.86781e-05; MAF= 0.00787%, 127/1614172 alleles, homozygotes = 3) and has highest observed frequency in the South Asian population (AF= 0.00135037; MAF= 0.13504%, 123/91086 alleles, homozygotes = 3); grpmax FAF= 0.00115569.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000171039; MAF= 0.01710%, 43/251404 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00137201; MAF= 0.13720%, 42/30612 alleles, homozygotes = 1); grpmax FAF= 0.00104332.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Uncertain significance (5 clinical laboratories). (ClinVarID = 184552)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.139. BayesDel score = -0.415893.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ATM, a kinase involved in the DNA damage response, is mutated in various solid and hematologic malignancies.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.