About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.6572+11C>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 v1.5.0. 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
BP4Supporting
BP4 · supporting
SpliceAI predicts no splicing impact for this intronic variant (max delta = 0.00). This meets the ATM VCEP BP4_Supporting threshold for splicing (SpliceAI ≤0.1).
BP7Supporting
BP7 · supporting
NM_000051.4:c.6572+11C>T is an intronic variant at position +11, which is further than +7 from the donor site. The ATM VCEP BP7 rule applies to deep intronic variants defined as further than (but not including) +7 at donor sites. SpliceAI predicts no splicing impact (max delta = 0.00), consistent with a lack of aberrant splicing.
Recorded classification: Likely benign
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: BP4 supporting, BP7 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
132 / 1,613,760 alleles
gnomAD v4.1: 132 / 1,613,760 alleles. Recorded AF 8.17965e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.95025e-05; MAF= 0.00495%, 14/282814 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000112867; MAF= 0.01129%, 4/35440 alleles, homozygotes = 0); grpmax FAF= 3.893e-05.
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
5 reported laboratory submissions
4 Likely benign · 1 Benign.
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 v1.5.0, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 6 not met · 5 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
NM_000051.4:c.6572+11C>T is an intronic variant located at position +11 in intron 45 of ATM, outside the canonical splice donor site. SpliceAI predicts no splicing impact (max delta score = 0.00), satisfying BP4 (supporting). The variant position at +11 is further than +7 from the donor site, meeting the ATM VCEP definition of a deep intronic variant for BP7 (supporting).
This variant is present in gnomAD v4.1 at an allele frequency of 0.00818% (132/1,613,760 alleles; grpmax FAF = 0.0102%) and in gnomAD v2.1 at 0.00495% (14/282,814 alleles). The frequency exceeds the VCEP PM2_Supporting threshold of ≤0.001% but does not reach BS1 (>0.05%) or BA1 (>0.5%) thresholds.
This variant has been reported in ClinVar as Likely benign by four clinical laboratories and as Benign by one clinical laboratory (ClinVar Variation ID: 490663). While ClinVar consensus favors a benign interpretation, the ATM VCEP does not permit use of BP6, and this evidence is noted for context only.
No functional studies, case-control data, segregation data, or de novo observations were identified for this variant. PVS1 is not applicable as the variant lies outside the canonical ±1,2 splice sites. PS1 cannot be applied without a PP3 baseline (SpliceAI <0.2).
Applying the ATM VCEP v1.5.0 ACMG/AMP combination rules: BP4_Supporting and BP7_Supporting are both met (2 benign supporting criteria). Rule 19 (≥2 Benign Supporting) yields a classification of Likely Benign.
No criteria match.
Met · 2
BP4 SupportingSpliceAI predicts no splicing impact for this intronic variant (max delta = 0.00). This meets the ATM VCEP BP4_Supporting threshold for splicing (SpliceAI ≤0.1). Details ▾Hide ▴
BP7 SupportingNM_000051.4:c.6572+11C>T is an intronic variant at position +11, which is further than +7 from the donor site. The ATM VCEP BP7 rule applies to deep intronic variants defined as further than (but not including) +7 at donor sites. SpliceAI predicts no splicing impact (max delta = 0.00), consistent with a lack of aberrant splicing. Details ▾Hide ▴
Evidence considered
- Intronic variant at +11
- further than +7 from donor site
- SpliceAI max delta = 0.00
- no aberrant splicing predicted
Sources
Not met · 6 · evaluated, threshold not reached
PVS1 NM_000051.4:c.6572+11C>T is an intronic variant at position +11, outside the canonical ±1,2 splice donor/acceptor dinucleotides. SpliceAI predicts no splicing impact (max delta = 0.00). The ATM VCEP PVS1 decision tree applies only to null variants (nonsense, frameshift, canonical ±1,2 splice sites); this variant does not qualify. Details ▾Hide ▴
Evidence considered
- Intronic variant at +11
- not at canonical ±1
- 2 splice site
- SpliceAI max delta = 0.00
- no predicted splicing impact
Sources
spliceai ↗vcep_atm_pvs1_1_5
PS1 The ATM PS1 splicing table requires a PP3 baseline (SpliceAI ≥0.2) for variants located outside donor/acceptor ±1,2 positions. SpliceAI max delta for this variant is 0.00, which does not meet PP3. Without a PP3 baseline, PS1 cannot be applied per the VCEP PS1 splicing framework. No known pathogenic variant at this nucleotide position with a matching predicted splicing event was identified. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- below PP3 threshold of 0.2
- No known pathogenic comparator at same nucleotide position
Sources
spliceai ↗vcep_atm_ps1_1_5
PM2 The ATM VCEP PM2_Supporting threshold is ≤0.001% (≤0.00001) in gnomAD v4. This variant has an allele frequency of 0.00818% (132/1,613,760 alleles) in gnomAD v4.1, which exceeds the VCEP PM2 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 0.00818% (132/1
- 613
- 760)
- exceeds VCEP PM2 threshold of ≤0.001%
Sources
PP3 The ATM VCEP PP3 threshold for splicing prediction is SpliceAI ≥0.2 for intronic variants outside donor/acceptor ±1,2 sites. SpliceAI max delta for this variant is 0.00, which does not meet the threshold. REVEL is not applicable as this is not a missense variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- below PP3 threshold of 0.2
- Not a missense variant
- REVEL not applicable
Sources
BA1 The ATM VCEP BA1 (Stand Alone) threshold is grpmax filtering AF >0.5% in gnomAD v4. The grpmax FAF for this variant is 0.0102%, far below the BA1 threshold. Details ▾Hide ▴
BS1 The ATM VCEP BS1 (Benign Strong) threshold is grpmax filtering AF >0.05% in gnomAD v4. The grpmax FAF for this variant is 0.0102%, which does not meet the BS1 threshold. Details ▾Hide ▴
Not assessed · 5 · no assessment recorded
PS3 No functional studies evaluating ATM kinase activity or radiosensitivity rescue for NM_000051.4:c.6572+11C>T were identified. The ATM VCEP PS3 framework requires demonstration that the variant fails to rescue ATM-specific features and/or radiosensitivity. Details ▾Hide ▴
Still missing
- No functional assay data available for this variant
Sources
2877900225741868
PS4 No case-control studies with adequate statistical power were identified for NM_000051.4:c.6572+11C>T. The ATM VCEP PS4_Strong requires case-control data with p≤0.05 and OR≥2 or lower 95% CI ≥1.5. Proband counting (PS4_Moderate) is explicitly excluded by the VCEP. Details ▾Hide ▴
Still missing
- No case-control data for this variant
PP1 No segregation data in affected relatives was identified for NM_000051.4:c.6572+11C>T. The ATM VCEP PP1 framework applies to autosomal recessive conditions (A-T) and requires observation in affected relatives. Details ▾Hide ▴
Still missing
- No segregation data available
BS3 No functional studies demonstrating rescue of ATM-specific features and/or radiosensitivity were identified for NM_000051.4:c.6572+11C>T. The ATM VCEP BS3 framework requires functional assay evidence. Details ▾Hide ▴
Still missing
- No functional assay data available for this variant
BP2 No proband data for unaffected individuals (≥18 years, no A-T) with this variant observed in trans or homozygous with a pathogenic/likely pathogenic ATM variant was identified. Assessment requires case-level data per the ATM PM3/BP2 point table. Details ▾Hide ▴
Still missing
- No proband-level data for BP2 assessment
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPATM VCEP specifies PS2 as not applicable: informative de novo occurrences have not been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PM1 VCEPATM VCEP specifies PM1 as not applicable: benign and pathogenic variants are known to occur within the same domains and germline mutational hotspots are not well defined. Details ▾Hide ▴
PM3 N/APM3 requires observation in trans with a pathogenic variant in A-T probands. No proband-level phase data was provided for NM_000051.4:c.6572+11C>T. Details ▾Hide ▴
Evidence considered
- No trans phase data available
- PM3 adjudication requires proband-level data per ATM PM3/BP2 table
Sources
PM4 N/AATM VCEP specifies PM4 for stop-loss variants only. NM_000051.4:c.6572+11C>T is an intronic substitution, not a stop-loss variant. Details ▾Hide ▴
PM5 N/AATM VCEP PM5_Supporting applies only to frameshifting/truncating variants with premature termination codons upstream of p.Arg3047, or splice variants where PVS1_VS(RNA) is applied based on observed splicing impact. This is an intronic variant at +11 with no predicted splicing impact (SpliceAI max delta = 0.00). Neither condition is met. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not frameshift/truncation
- SpliceAI max delta = 0.00
- no PVS1_VS(RNA) applicable
Sources
PM6 VCEPATM VCEP specifies PM6 as not applicable for both AD and AR disease: informative de novo occurrences have not been observed. Details ▾Hide ▴
PP2 VCEPATM VCEP specifies PP2 as not applicable: ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
PP4 VCEPATM VCEP specifies PP4 as not applicable for both AD and AR disease: breast cancer has multiple genetic etiologies (genetic heterogeneity), and A-T evidence is built into the PM3/BP2 table. Details ▾Hide ▴
PP5 VCEPATM VCEP specifies PP5 as not applicable. Details ▾Hide ▴
BS2 VCEPATM VCEP specifies BS2 as not applicable. Details ▾Hide ▴
BS4 VCEPATM VCEP specifies BS4 as not applicable. Details ▾Hide ▴
BP1 VCEPATM VCEP specifies BP1 as not applicable. Details ▾Hide ▴
BP3 VCEPATM VCEP specifies BP3 as not applicable. Details ▾Hide ▴
BP5 VCEPATM VCEP specifies BP5 as not applicable: cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and ATM has low penetrance. Details ▾Hide ▴
BP6 VCEPATM VCEP specifies BP6 as not applicable for this VCEP, per ClinGen SVI VCEP Review Committee recommendation. Details ▾Hide ▴
PS5 N/APS5 is not included in the ATM VCEP v1.5.0 criteria framework. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.6572+11C>T
- Protein (HGVS p.)
- NP_000042.3:p.?
- GRCh38
- chr11:108321431 C>T
- GRCh37
- chr11:108192158 C>T
- ClinVar
- 490663
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
132 / 1,613,760 alleles
AF 8.18e-05 · 0 homozygotes · FAF 0.000102
gnomAD v2.1
14 / 282,814 alleles
AF 4.95e-05 · 0 homozygotes · FAF 3.89e-05
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 8.2e-05 · 132 / 1,613,760 alleles · 0 hom · FAF 0.0001
| Admixed American11 / 59,982 | 0.00018 |
| European (non-Finnish)110 / 1,179,928 | 9.3e-05 |
| African/African American4 / 74,860 | 5.3e-05 |
| East Asian2 / 44,882 | 4.5e-05 |
| South Asian3 / 91,070 | 3.3e-05 |
| Remaining individuals1 / 62,476 | 1.6e-05 |
| European (Finnish)1 / 63,968 | 1.6e-05 |
0 alternate alleles recorded in 3 other groups: Amish, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 5e-05 · 14 / 282,814 alleles · 0 hom · FAF 3.9e-05
| Admixed American4 / 35,440 | 0.00011 |
| European (non-Finnish)9 / 129,148 | 7e-05 |
| African/African American1 / 24,956 | 4e-05 |
0 alternate alleles recorded in 5 other groups: Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 8.17965e-05; MAF= 0.00818%, 132/1613760 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000183388; MAF= 0.01834%, 11/59982 alleles, homozygotes = 0); grpmax FAF= 0.00010205.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.95025e-05; MAF= 0.00495%, 14/282814 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000112867; MAF= 0.01129%, 4/35440 alleles, homozygotes = 0); grpmax FAF= 3.893e-05.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingSpliceAI predicts no splicing impact for this intronic variant (max delta = 0.00). This meets the ATM VCEP BP4_Supporting threshold for splicing (SpliceAI ≤0.1). Details ▾Hide ▴
BP7 SupportingNM_000051.4:c.6572+11C>T is an intronic variant at position +11, which is further than +7 from the donor site. The ATM VCEP BP7 rule applies to deep intronic variants defined as further than (but not including) +7 at donor sites. SpliceAI predicts no splicing impact (max delta = 0.00), consistent with a lack of aberrant splicing. Details ▾Hide ▴
Evidence considered
- Intronic variant at +11
- further than +7 from donor site
- SpliceAI max delta = 0.00
- no aberrant splicing predicted
Sources
PP3 The ATM VCEP PP3 threshold for splicing prediction is SpliceAI ≥0.2 for intronic variants outside donor/acceptor ±1,2 sites. SpliceAI max delta for this variant is 0.00, which does not meet the threshold. REVEL is not applicable as this is not a missense variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- below PP3 threshold of 0.2
- Not a missense variant
- REVEL not applicable
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
10 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.No paper-specific finding is recorded.
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PMID 28779002 ↗Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.Decker B et al. · 2017No paper-specific finding is recorded.
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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.No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
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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. · 2007No paper-specific finding is recorded.
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008No paper-specific finding is recorded.
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PMID 20301317 ↗PMID:20301317No paper-specific finding is recorded.
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20050888 ↗EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.No paper-specific finding is recorded.
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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
132 / 1,613,760 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
4 Likely benign · 1 Benign
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/variation/490663/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108192158-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108321431-C-T?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.6572…
- OncoKB ↗www.oncokb.org/gene/ATM/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.6572+11C%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= 8.17965e-05; MAF= 0.00818%, 132/1613760 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000183388; MAF= 0.01834%, 11/59982 alleles, homozygotes = 0); grpmax FAF= 0.00010205.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.95025e-05; MAF= 0.00495%, 14/282814 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000112867; MAF= 0.01129%, 4/35440 alleles, homozygotes = 0); grpmax FAF= 3.893e-05.
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 490663)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).