About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.8787-26C>T, p.?
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. 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
BP4Supporting
BP4 · supporting
The ATM VCEP BP4 rule for splicing variants is met when SpliceAI predicts no splicing impact (delta score ≤0.1). SpliceAI max delta score for NM_000051.4:c.8787-26C>T is 0.04, which satisfies the ≤0.1 threshold. Multiple lines of computational evidence suggest no impact on splicing.
BP7Supporting
BP7 · supporting
The ATM VCEP BP7 rule applies to deep intronic variants located further than (but not including) -21 at the acceptor site. NM_000051.4:c.8787-26C>T is at position -26 relative to exon 60, which is beyond the -21 threshold. The variant is a deep intronic substitution with no predicted splice impact (SpliceAI max delta 0.04), consistent with a benign computational profile.
Recorded classification: Likely benign
ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ATM Version 1.5 v1.5 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: BP4 supporting benign, BP7 supporting benign; 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
178 / 1,598,370 alleles
gnomAD v4.1: 178 / 1,598,370 alleles. Recorded AF 0.000111363. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.01302e-05; MAF= 0.00601%, 17/282720 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000138619; MAF= 0.01386%, 1/7214 alleles, homozygotes = 0); grpmax FAF= 4.442e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.040 maximum delta
Recorded SpliceAI maximum delta score: 0.040. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under ClinGen ATM VCEP v1.5, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 12 not met · 0 not assessed · 15 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000051.4:c.8787-26C>T is a deep intronic variant located 26 nucleotides upstream of exon 60 in ATM. SpliceAI predicts no significant splice impact (max delta score 0.04).
BP7 (supporting) is applied per the ATM VCEP v1.5: the variant is intronic at position -26, which is further than the -21 acceptor site threshold for deep intronic variants.
BP4 (supporting) is applied per the ATM VCEP v1.5: SpliceAI predicts no splicing impact (max delta 0.04 ≤ 0.1 threshold).
The variant is present in gnomAD v4.1 at an allele frequency of 0.01114% (178/1,598,370 alleles) with no homozygotes. This frequency is above the VCEP PM2 threshold of ≤0.001% but below BS1 (>0.05%) and BA1 (>0.5%) thresholds.
The variant is absent from ClinVar, COSMIC, and the published literature. No functional studies, segregation data, or case-control studies are available.
Two supporting benign criteria are met (BP7, BP4) with no pathogenic criteria met. Per ACMG/AMP 2015 combination rules, ≥2 benign supporting criteria results in a classification of Likely Benign (Rule 19).
No criteria match.
Met · 2
BP4 SupportingThe ATM VCEP BP4 rule for splicing variants is met when SpliceAI predicts no splicing impact (delta score ≤0.1). SpliceAI max delta score for NM_000051.4:c.8787-26C>T is 0.04, which satisfies the ≤0.1 threshold. Multiple lines of computational evidence suggest no impact on splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.04
- VCEP BP4 splicing threshold: ≤0.1 — satisfied
Sources
BP7 SupportingThe ATM VCEP BP7 rule applies to deep intronic variants located further than (but not including) -21 at the acceptor site. NM_000051.4:c.8787-26C>T is at position -26 relative to exon 60, which is beyond the -21 threshold. The variant is a deep intronic substitution with no predicted splice impact (SpliceAI max delta 0.04), consistent with a benign computational profile. Details ▾Hide ▴
Evidence considered
- Variant is at intronic position -26
- beyond the VCEP BP7 cutoff of -21
- SpliceAI max delta 0.04
- no predicted cryptic splice site creation or disruption
Sources
Not met · 12 · evaluated, threshold not reached
PVS1 NM_000051.4:c.8787-26C>T is a deep intronic variant located 26 nucleotides upstream of exon 60. It does not involve a canonical ±1,2 splice site, is not a nonsense, frameshift, initiation codon, or exon deletion variant. SpliceAI predicts no significant splice impact (max delta score 0.04). No RNA evidence of aberrant splicing is available. The variant does not meet the ATM VCEP PVS1 decision tree entry criteria for a predicted or observed null variant. Details ▾Hide ▴
Evidence considered
- Deep intronic variant at c.8787-26
- not a canonical splice site
- SpliceAI max delta score 0.04
- no predicted splice impact
- VCEP PVS1 decision tree requires canonical ±1
- 2 splice site or predicted/observed splice defect for intronic variants
Sources
PS1 PS1 is applicable only when a different nucleotide change at the same position has been established as pathogenic with the same predicted functional outcome. For intronic/splicing variants, the ATM VCEP PS1 splicing table requires a comparator P/LP reference variant at the same nucleotide or within the same donor/acceptor motif with matching predicted splice events. No such comparator variant has been identified for c.8787-26C>T, and SpliceAI predicts no splice impact (max delta 0.04), leaving no baseline prediction to match against a comparator. Details ▾Hide ▴
Evidence considered
- No comparator pathogenic/likely pathogenic variant identified at the same nucleotide position
- SpliceAI max delta 0.04 indicates no predicted splice event to match against a reference variant
Sources
spliceai ↗vcep_atm_ps1_1_5
PS3 No functional data are available for NM_000051.4:c.8787-26C>T. The variant was not identified in the ATM VCEP functional assay spreadsheets (Suppl_TableS1_PMID 40580951, clingen_hbop_atm_supplementary_tables_1_and_2_v1). No literature reports variant-specific functional characterization. The variant is absent from ClinVar, COSMIC, and OncoKB. SpliceAI predicts no splicing impact (max delta 0.04), and no RNA studies have been performed. Details ▾Hide ▴
Evidence considered
- Variant absent from ATM VCEP functional assay spreadsheets
- No literature-based functional characterization identified
- SpliceAI max delta 0.04
- no predicted functional impact
Still missing
- No functional studies have evaluated this specific variant
Sources
vcep_suppl_tables1_pmid_40580951vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1spliceai ↗clinvar ↗
PS4 The ATM VCEP requires case-control studies with p-value ≤0.05 and OR/HR/RR ≥2 or lower 95% CI ≥1.5. No case-control data are available for this variant. The variant has not been reported in ClinVar or the literature in association with disease. Details ▾Hide ▴
PM2 The ATM VCEP PM2 threshold requires allele frequency ≤0.001% in gnomAD v4. This variant has an overall allele frequency of 0.01114% (178/1,598,370 alleles) in gnomAD v4.1, which exceeds the VCEP threshold. PM2 is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 178/1
- 598
- 370 alleles (AF = 0.01114%)
- VCEP PM2 threshold: ≤0.001% — not satisfied
Sources
PM5 The ATM VCEP PM5 rule applies only to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, or to splice variants with PVS1_VS(RNA) applied based on observed splicing impact. NM_000051.4:c.8787-26C>T is a deep intronic substitution, not a frameshift/truncation variant, and PVS1 is not applied. The variant type does not satisfy the VCEP PM5 rule. Details ▾Hide ▴
Evidence considered
- Variant is a deep intronic substitution
- not a frameshift/truncation
- PVS1 not applied
- no PVS1_VS(RNA) evidence
Sources
cspec ↗pm5_candidates
PP1 No segregation data are available for this variant. The variant has not been reported in any families or probands. Details ▾Hide ▴
PP3 The ATM VCEP PP3 rule for splicing variants requires a SpliceAI delta score ≥0.2. SpliceAI predicts no significant splice impact for this variant (max delta score 0.04), which is below the VCEP threshold. PP3 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.04
- VCEP PP3 splicing threshold: ≥0.2 — not satisfied
Sources
BA1 The ATM VCEP BA1 rule requires a grpmax filtering allele frequency >0.5% in gnomAD v4. The grpmax FAF for this variant is 0.0115% (0.00011482), which is well below the stand-alone benign threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF: 0.00011482 (0.0115%)
- VCEP BA1 threshold: >0.5% — not satisfied
Sources
BS1 The ATM VCEP BS1 rule requires a grpmax filtering allele frequency >0.05% in gnomAD v4. The grpmax FAF for this variant is 0.0115% (0.00011482), which is below the strong benign threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF: 0.00011482 (0.0115%)
- VCEP BS1 threshold: >0.05% — not satisfied
Sources
BS3 The ATM VCEP BS3 rule requires functional evidence that the variant rescues ATM-specific features and/or radiosensitivity. No functional studies have been performed on this variant. The variant was not identified in the VCEP functional assay spreadsheets, and no literature reports functional characterization. Details ▾Hide ▴
Evidence considered
- Variant absent from ATM VCEP kinase activity and radiosensitivity assay spreadsheets
- No functional rescue data available
Still missing
- No functional studies have evaluated this variant
Sources
BP2 No proband data are available to assess BP2. The ATM VCEP BP2 rule requires A-T proband data with trans or homozygous configuration in unaffected individuals. No such data have been reported for this variant. Details ▾Hide ▴
Evidence considered
- No A-T probands reported for this variant
- No trans or homozygous configuration data in unaffected individuals
Sources
cspec ↗vcep_atm_pm3_bp2_1_5
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPThe ATM VCEP deems PS2 not applicable: informative de novo occurrences have not yet been observed for ATM, and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PM1 VCEPThe ATM VCEP deems PM1 not applicable: benign and pathogenic variants are known to occur within the same domains and germline mutational hotspots are not well defined at this time. Details ▾Hide ▴
Sources
PM3 N/APM3 assessment requires A-T proband data with trans configuration. No proband data are available for this variant, and this criterion was prescreened as trivially not applicable for this case. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to stop-loss variants or in-frame deletions/insertions. This is a single-nucleotide intronic substitution, not a protein-length-altering variant. Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPThe ATM VCEP deems PM6 not applicable: informative de novo occurrences have not yet been observed for ATM, and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PP2 VCEPThe ATM VCEP deems PP2 not applicable: ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
Sources
PP4 VCEPThe ATM VCEP deems PP4 not applicable: for autosomal dominant disease, breast cancer has multiple genetic etiologies with no features readily distinguishing hereditary from sporadic causes; for autosomal recessive disease, such evidence is built into the A-T PM3/BP2 table. Details ▾Hide ▴
Sources
PP5 VCEPThe ATM VCEP deems PP5 not applicable for this VCEP, and the variant is absent from ClinVar with no expert panel classifications to review. Details ▾Hide ▴
BS2 VCEPBS2 is not defined for use in the ATM VCEP (ClinGen HBOP v1.5) framework. The VCEP criteria set declares BS2 not applicable. Details ▾Hide ▴
Sources
BS4 VCEPBS4 is not defined for use in the ATM VCEP (ClinGen HBOP v1.5) framework. The VCEP criteria set declares BS4 not applicable. Details ▾Hide ▴
Sources
BP1 VCEPThe ATM VCEP deems BP1 not applicable. Details ▾Hide ▴
Sources
BP3 VCEPBP3 applies to in-frame deletions/insertions in repetitive regions without known function. This is a single-nucleotide substitution, not an in-frame indel. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPThe ATM VCEP deems BP5 not applicable: cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and ATM has low penetrance with higher tolerance in the general population. Details ▾Hide ▴
Sources
BP6 VCEPThe ATM VCEP deems BP6 not applicable for this VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Additionally, the variant is absent from ClinVar with no benign classifications to review. Details ▾Hide ▴
PS5 N/APS5 is not defined in the ATM VCEP (ClinGen HBOP v1.5) framework. The VCEP criteria set does not include PS5 specifications. Details ▾Hide ▴
Sources
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.8787-26C>T
- Protein (HGVS p.)
- NP_000042.3:p.?
- GRCh38
- chr11:108354785 C>T
- GRCh37
- chr11:108225512 C>T
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
178 / 1,598,370 alleles
AF 0.000111 · 0 homozygotes · FAF 0.000115
gnomAD v2.1
17 / 282,720 alleles
AF 6.01e-05 · 0 homozygotes · FAF 4.44e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00011 · 178 / 1,598,370 alleles · 0 hom · FAF 0.00011
| European (non-Finnish)154 / 1,165,954 | 0.00013 |
| South Asian10 / 90,750 | 0.00011 |
| Remaining individuals6 / 61,950 | 9.7e-05 |
| Admixed American5 / 59,982 | 8.3e-05 |
| African/African American2 / 74,516 | 2.7e-05 |
| East Asian1 / 44,788 | 2.2e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 6e-05 · 17 / 282,720 alleles · 0 hom · FAF 4.4e-05
| Remaining individuals1 / 7,214 | 0.00014 |
| South Asian4 / 30,614 | 0.00013 |
| European (non-Finnish)9 / 129,092 | 7e-05 |
| Admixed American2 / 35,436 | 5.6e-05 |
| African/African American1 / 24,970 | 4e-05 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, East Asian, European (Finnish).
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000111363; MAF= 0.01114%, 178/1598370 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000132081; MAF= 0.01321%, 154/1165954 alleles, homozygotes = 0); grpmax FAF= 0.00011482.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.01302e-05; MAF= 0.00601%, 17/282720 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000138619; MAF= 0.01386%, 1/7214 alleles, homozygotes = 0); grpmax FAF= 4.442e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingThe ATM VCEP BP4 rule for splicing variants is met when SpliceAI predicts no splicing impact (delta score ≤0.1). SpliceAI max delta score for NM_000051.4:c.8787-26C>T is 0.04, which satisfies the ≤0.1 threshold. Multiple lines of computational evidence suggest no impact on splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.04
- VCEP BP4 splicing threshold: ≤0.1 — satisfied
Sources
BP7 SupportingThe ATM VCEP BP7 rule applies to deep intronic variants located further than (but not including) -21 at the acceptor site. NM_000051.4:c.8787-26C>T is at position -26 relative to exon 60, which is beyond the -21 threshold. The variant is a deep intronic substitution with no predicted splice impact (SpliceAI max delta 0.04), consistent with a benign computational profile. Details ▾Hide ▴
Evidence considered
- Variant is at intronic position -26
- beyond the VCEP BP7 cutoff of -21
- SpliceAI max delta 0.04
- no predicted cryptic splice site creation or disruption
Sources
PP3 The ATM VCEP PP3 rule for splicing variants requires a SpliceAI delta score ≥0.2. SpliceAI predicts no significant splice impact for this variant (max delta score 0.04), which is below the VCEP threshold. PP3 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.04
- VCEP PP3 splicing threshold: ≥0.2 — not satisfied
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
178 / 1,598,370 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.040
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC 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/?term=NM_000051.4%3Ac.8787-26C%3ET
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108225512-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108354785-C-T?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108354785-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.8787…
- OncoKB ↗www.oncokb.org/gene/ATM/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.8787-26C%3ET
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= 0.000111363; MAF= 0.01114%, 178/1598370 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000132081; MAF= 0.01321%, 154/1165954 alleles, homozygotes = 0); grpmax FAF= 0.00011482.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.01302e-05; MAF= 0.00601%, 17/282720 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000138619; MAF= 0.01386%, 1/7214 alleles, homozygotes = 0); grpmax FAF= 4.442e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).