About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.8315del, p.(Gly2772GlufsTer34)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Very strong
PVS1 · very strong
This variant is a frameshift deletion, NM_000051.4:c.8315del, predicted to cause p.(Gly2772GlufsTer34). ATM-specific guidance permits PVS1 for loss-of-function variants, and this variant is not in a context that would withhold PVS1 under the available ATM loss-of-function framework.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v4.1 and gnomAD v2.1. The observed population frequency is 0%, which is below the ATM PM2_Supporting threshold of less than or equal to 0.001% in gnomAD v4.
PM5Supporting
PM5 · supporting
ATM-specific guidance allows PM5_Supporting for truncating variants with premature termination codons upstream of p.Arg3047. This variant causes p.(Gly2772GlufsTer34), which truncates the protein upstream of p.Arg3047 and therefore meets that ATM-specific positional rule.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule4 (1 Pathogenic.Very Strong + Pathogenic.Supporting >=2) with applied criteria: PVS1 very strong, PM2 supporting, PM5 supporting; maps to Pathogenic.
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
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.
28 criteria with recorded statuses: 3 met · 4 not met · 6 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
The ATM c.8315del (p.Gly2772GlufsTer34) variant has been reported in ClinVar with pathogenic and likely pathogenic clinical submissions.
This variant is absent from gnomAD v4.1 and gnomAD v2.1, supporting rarity in the general population.
ATM-specific criteria support pathogenic evidence for this truncating variant because p.(Gly2772GlufsTer34) introduces a premature termination codon upstream of the p.Arg3047 threshold used for ATM truncating variants, and ATM loss of function is an established disease mechanism.
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.14.
No criteria match.
Met · 3
PVS1 Very strongThis variant is a frameshift deletion, NM_000051.4:c.8315del, predicted to cause p.(Gly2772GlufsTer34). ATM-specific guidance permits PVS1 for loss-of-function variants, and this variant is not in a context that would withhold PVS1 under the available ATM loss-of-function framework. Details ▾Hide ▴
Rule
ATM PVS1 decision tree for loss-of-function variants
Evidence considered
- Frameshift consequence p.(Gly2772GlufsTer34)
- ATM loss of function is an established disease mechanism
- ATM PVS1 guidance is applicable
Sources
PM2 SupportingThis variant is absent from gnomAD v4.1 and gnomAD v2.1. The observed population frequency is 0%, which is below the ATM PM2_Supporting threshold of less than or equal to 0.001% in gnomAD v4. Details ▾Hide ▴
Rule
PM2_Supporting if frequency is <=0.001% in gnomAD v4
Evidence considered
- Absent from gnomAD v4.1
- Absent from gnomAD v2.1
Sources
PM5 SupportingATM-specific guidance allows PM5_Supporting for truncating variants with premature termination codons upstream of p.Arg3047. This variant causes p.(Gly2772GlufsTer34), which truncates the protein upstream of p.Arg3047 and therefore meets that ATM-specific positional rule. Details ▾Hide ▴
Rule
PM5_Supporting for frameshifting or truncating variants with premature termination codons upstream of p.Arg3047
Evidence considered
- Predicted truncation at codon 2772 with premature termination 34 residues downstream
- ATM truncating-variant rule uses p.Arg3047 as the C-terminal threshold
Sources
Not met · 4 · evaluated, threshold not reached
PP3 SpliceAI predicts a maximum delta score of 0.14. This value is below the ATM PP3 splicing threshold of greater than or equal to 0.2, so available computational splicing evidence does not support PP3 for this variant. Details ▾Hide ▴
Rule
PP3 for splicing requires SpliceAI >=0.2
Evidence considered
- SpliceAI max delta score 0.14
Sources
BA1 This variant is absent from gnomAD v4.1. The observed population frequency is 0%, which is below the ATM BA1 threshold of greater than 0.5%. Details ▾Hide ▴
Rule
BA1 if grpmax filtering AF >0.5% in gnomAD v4
Evidence considered
- Absent from gnomAD v4.1
Sources
BS1 This variant is absent from gnomAD v4.1. The observed population frequency is 0%, which is below the ATM BS1 threshold of greater than 0.05%. Details ▾Hide ▴
Rule
BS1 if grpmax filtering AF >0.05% in gnomAD v4
Evidence considered
- Absent from gnomAD v4.1
Sources
BP4 SpliceAI predicts no significant splice impact with a maximum delta score of 0.14, but this value is above the ATM BP4 splicing threshold of less than or equal to 0.1. The variant is also a frameshift rather than a missense change for REVEL-based assessment. Details ▾Hide ▴
Rule
BP4 for splicing requires SpliceAI <=0.1
Evidence considered
- SpliceAI max delta score 0.14
Sources
Not assessed · 6 · no assessment recorded
PS3 ATM-specific functional criteria require a validated assay showing failure to rescue ATM-specific function, with or without radiosensitivity depending on strength. Available sources cited functional literature, but no variant-specific ATM assay result meeting these PS3 requirements was identified for this variant. Details ▾Hide ▴
Rule
PS3_Supporting or PS3_Moderate requires qualifying ATM-specific non-rescue data
Evidence considered
- ATM-specific PS3 framework reviewed
- Functional literature references reviewed
- No variant-specific qualifying PS3 result identified
Still missing
- Variant-specific damaging functional assay data were not identified.
Sources
PS4 This variant has been reported in ClinVar, but no case-control study data were identified showing a p-value less than or equal to 0.05 together with an odds ratio, hazard ratio, or relative risk of at least 2, or a lower 95% confidence interval of at least 1.5. Therefore PS4 is not established from the available evidence. Details ▾Hide ▴
PM3 ATM-specific PM3 requires qualifying observations in trans with a pathogenic or likely pathogenic ATM variant, scored under the ATM PM3/BP2 point framework. No qualifying phase-confirmed or point-scored recessive observations were identified for this variant. Details ▾Hide ▴
Rule
PM3 strength depends on ATM PM3/BP2 point totals
Evidence considered
- ATM PM3/BP2 point framework reviewed
- No qualifying PM3 observations identified
Still missing
- No qualifying in-trans observations with a pathogenic or likely pathogenic ATM variant were identified.
Sources
cspec ↗vcep_a_t_m___p_m_3___b_p_2___1___5
PP1 ATM-specific PP1 requires segregation data in affected relatives for the recessive condition framework. No qualifying segregation data were identified for this variant. Details ▾Hide ▴
Rule
PP1 strength depends on the number of affected relatives in the AR framework
Evidence considered
- ATM segregation framework reviewed
- No qualifying segregation observations identified
Still missing
- No informative family segregation data were identified.
Sources
BS3 ATM-specific functional criteria require a validated rescue assay showing rescue of ATM-specific function and/or radiosensitivity. No variant-specific rescue data meeting these ATM BS3 requirements were identified for this variant. Details ▾Hide ▴
Rule
BS3_Supporting or BS3_Moderate requires qualifying rescue data in ATM-specific assays
Evidence considered
- ATM-specific BS3 framework reviewed
- No variant-specific qualifying rescue result identified
Still missing
- Variant-specific benign functional rescue data were not identified.
Sources
BP2 ATM-specific BP2 requires documented co-occurrence in trans or homozygosity in an unaffected person under the ATM PM3/BP2 point framework. No qualifying phase or unaffected co-occurrence data were identified for this variant. Details ▾Hide ▴
Rule
BP2 strength depends on ATM PM3/BP2 point totals
Evidence considered
- ATM PM3/BP2 point framework reviewed
- No qualifying BP2 observations identified
Still missing
- No qualifying unaffected in-trans
- cis
- or homozygous observation data were identified.
Sources
cspec ↗vcep_a_t_m___p_m_3___b_p_2___1___5
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 is intended for the same amino acid change as a known pathogenic variant or for defined splice-event matches in the ATM PS1 splicing framework. This variant is a frameshift deletion, and no same-effect PS1 match was identified. Details ▾Hide ▴
Evidence considered
- ATM PS1 framework reviewed
- Variant type is frameshift deletion
Sources
cspec ↗vcep_a_t_m___p_s_1___1___5
PS2 N/AAvailable ATM-specific specifications do not use PS2 for ATM. Details ▾Hide ▴
PM1 N/AAvailable ATM-specific specifications do not use PM1 because germline mutational hotspots are not sufficiently defined for ATM. Details ▾Hide ▴
Evidence considered
- ATM VCEP marks PM1 not applicable
- No significant hotspot evidence identified
Sources
PM4 N/AATM-specific PM4 is reserved for stop-loss variants. This variant is a frameshift deletion, so PM4 does not apply. Details ▾Hide ▴
PM6 N/AAvailable ATM-specific specifications do not use PM6 for ATM. Details ▾Hide ▴
PP2 N/AAvailable ATM-specific specifications do not use PP2 because ATM does not have a sufficiently constrained missense profile for this rule. Details ▾Hide ▴
PP4 N/AAvailable ATM-specific specifications do not use PP4 as an independent line of evidence for ATM. Details ▾Hide ▴
PP5 N/AAvailable ATM-specific specifications do not use PP5. Details ▾Hide ▴
BS2 N/AAvailable ATM-specific specifications do not use BS2 because ATM-related disease shows incomplete penetrance. Details ▾Hide ▴
BS4 N/AAvailable ATM-specific specifications do not use BS4 for ATM because segregation analysis is not considered reliable for this low-penetrance context, and lack of segregation in A-T families is not assigned independent weight. Details ▾Hide ▴
BP1 N/AAvailable ATM-specific specifications do not use BP1 because pathogenic missense variants are known in ATM. Details ▾Hide ▴
BP3 N/AAvailable ATM-specific specifications do not use BP3. Details ▾Hide ▴
BP5 N/AAvailable ATM-specific specifications do not use BP5. Details ▾Hide ▴
BP6 N/AAvailable ATM-specific specifications do not use BP6. Details ▾Hide ▴
BP7 N/ABP7 is reserved for synonymous or deep intronic variants, or for RNA studies showing lack of splice defect in those variant classes. This variant is an exonic frameshift deletion, so BP7 does not apply. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.8315del
- Protein (HGVS p.)
- NP_000042.3:p.(Gly2772GlufsTer34)
- GRCh38
- chr11:108343266 AG>A
- GRCh37
- chr11:108213993 AG>A
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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 SpliceAI predicts a maximum delta score of 0.14. This value is below the ATM PP3 splicing threshold of greater than or equal to 0.2, so available computational splicing evidence does not support PP3 for this variant. Details ▾Hide ▴
Rule
PP3 for splicing requires SpliceAI >=0.2
Evidence considered
- SpliceAI max delta score 0.14
Sources
BP4 SpliceAI predicts no significant splice impact with a maximum delta score of 0.14, but this value is above the ATM BP4 splicing threshold of less than or equal to 0.1. The variant is also a frameshift rather than a missense change for REVEL-based assessment. Details ▾Hide ▴
Rule
BP4 for splicing requires SpliceAI <=0.1
Evidence considered
- SpliceAI max delta score 0.14
Sources
BP7 N/ABP7 is reserved for synonymous or deep intronic variants, or for RNA studies showing lack of splice defect in those variant classes. This variant is an exonic frameshift deletion, so BP7 does not apply. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.14).
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
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
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/2506475/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108213993-AG-A?dataset=gno…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108343266-AG-A?dataset=…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.8315…
- OncoKB ↗www.oncokb.org/gene/ATM/G2772Efs*34
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=105165636
- 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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Pathogenic (2 clinical laboratories) and as Likely pathogenic (1 clinical laboratory).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.14).
Functional
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV53726306, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.