About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.6059G>T, p.(Gly2020Val)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v4.1 and gnomAD v2.1. A frequency of 0% is below the ATM PM2_Supporting threshold of ≤0.001% in gnomAD v4, supporting PM2_Supporting.
PP3Supporting
PP3 · supporting
In silico evidence supports a deleterious effect for this missense variant because the REVEL score is 0.753, which is above the ATM PP3 threshold of >0.7333. SpliceAI predicts no meaningful splice effect with a max delta score of 0.02, supporting interpretation as a missense change rather than a splice-altering variant.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
ATM HBOP CSPEC/VCEP criteria-combination framework (cspec_ruleset v1.5.0; Richards et al. 2015 combining rules as instantiated in the retrieved final classification framework).
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.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: 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
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: 2 met · 6 not met · 4 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 ATM c.6059G>T (p.Gly2020Val) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar as a variant of uncertain significance with multiple clinical laboratory submissions.
This variant is absent from gnomAD v2.1 and gnomAD v4.1, which is below the ATM PM2_Supporting threshold of 0.001% in gnomAD v4.
An ATM supplementary functional dataset classified this variant as non-functional, but the available evidence does not document the ATM VCEP-required rescue assay endpoints needed to apply PS3 or BS3.
In silico evidence supports a deleterious missense effect because REVEL is 0.753, which is above the ATM PP3 threshold of 0.7333, while SpliceAI predicts no meaningful splice impact with a maximum delta score of 0.02.
No criteria match.
Met · 2
PM2 SupportingThis variant is absent from gnomAD v4.1 and gnomAD v2.1. A frequency of 0% is below the ATM PM2_Supporting threshold of ≤0.001% in gnomAD v4, supporting PM2_Supporting. Details ▾Hide ▴
Rule
ATM PM2_Supporting: frequency ≤0.001% in gnomAD v4 dataset.
Evidence considered
- gnomAD v4.1: absent
- gnomAD v2.1: absent
Sources
PP3 SupportingIn silico evidence supports a deleterious effect for this missense variant because the REVEL score is 0.753, which is above the ATM PP3 threshold of >0.7333. SpliceAI predicts no meaningful splice effect with a max delta score of 0.02, supporting interpretation as a missense change rather than a splice-altering variant. Details ▾Hide ▴
Rule
ATM PP3 for missense variants: REVEL >0.7333.
Evidence considered
- REVEL = 0.753
- SpliceAI max delta score = 0.02
Sources
Not met · 6 · evaluated, threshold not reached
PS1 No pathogenic or likely pathogenic ATM variant producing the same amino acid change was identified, and SpliceAI does not suggest a splice effect that would support use of the ATM PS1 splicing table. Available evidence does not support PS1. Details ▾Hide ▴
Rule
ATM PS1 requires the same amino acid change as an established pathogenic/likely pathogenic variant, with splicing ruled out for both alterations.
Evidence considered
- ClinVar variation 955939 is the current p.(Gly2020Val) entry
- No alternate pathogenic/likely pathogenic same-protein-change ATM variant was identified in ClinVar
- SpliceAI max delta score = 0.02
Sources
PS3 An ATM supplementary functional dataset listed this variant as non-functional, but the available evidence does not document the ATM VCEP-required rescue assay endpoints showing failure to rescue both an ATM-specific feature and radiosensitivity. The available data are therefore insufficient to apply PS3. Details ▾Hide ▴
Rule
ATM PS3_Moderate requires failure to rescue both an ATM-specific feature and radiosensitivity; PS3_Supporting requires failure to rescue an ATM-specific feature only.
Evidence considered
- Suppl_TableS1_PMID 40580951.xlsx row for c.6059G>T / G2020V: Classification=Non-functional, Confidence=High
- ATM CSPEC PS3 requires failure to rescue defined ATM-specific functional endpoints
Still missing
- No qualifying ATM rescue assay documenting failure to rescue both an ATM-specific feature and radiosensitivity was identified.
Sources
BA1 This variant is absent from gnomAD v4.1. A frequency of 0% is below the ATM BA1 threshold of >0.5%, so BA1 is not met. Details ▾Hide ▴
Rule
ATM BA1: grpmax filtering allele frequency >0.5% in gnomAD v4.
Evidence considered
- gnomAD v4.1: absent
Sources
BS1 This variant is absent from gnomAD v4.1. A frequency of 0% is below the ATM BS1 threshold of >0.05%, so BS1 is not met. Details ▾Hide ▴
Rule
ATM BS1: grpmax filtering allele frequency >0.05% in gnomAD v4.
Evidence considered
- gnomAD v4.1: absent
Sources
BS3 No study was identified showing that this variant rescues an ATM-specific functional defect or radiosensitivity. The available supplementary functional dataset does not provide the ATM VCEP-required rescue assay evidence, so BS3 is not met. Details ▾Hide ▴
Rule
ATM BS3 requires rescue of an ATM-specific feature and/or radiosensitivity, with higher weight when both are rescued.
Evidence considered
- Suppl_TableS1_PMID 40580951.xlsx includes a non-functional classification but not VCEP-defined rescue endpoints
Still missing
- No qualifying rescue assay data were identified.
Sources
BP4 Benign computational evidence is not supported because the REVEL score is 0.753, which is above the ATM BP4 missense threshold of ≤0.249. Although SpliceAI is low at 0.02 and does not predict splice disruption, the missense prediction does not support BP4. Details ▾Hide ▴
Rule
ATM BP4 for missense variants: REVEL ≤0.249; for splicing, SpliceAI ≤0.1 supports no splice impact.
Evidence considered
- REVEL = 0.753
- SpliceAI max delta score = 0.02
Sources
Not assessed · 4 · no assessment recorded
PS4 No case-control study or other quantitative enrichment data were identified showing this variant is significantly enriched in affected individuals. Available evidence does not support application of PS4 at this time. Details ▾Hide ▴
Rule
ATM PS4 requires case-control evidence with p-value ≤0.05 and effect size ≥2 or lower 95% CI ≥1.5.
Evidence considered
- Literature packet did not provide variant-specific case-control enrichment data
- ClinVar shows VUS submissions only
Still missing
- No qualifying case-control statistics were identified.
- No odds ratio, hazard ratio, relative risk, or lower 95% confidence interval meeting ATM PS4 thresholds was identified.
Sources
PM3 No evidence was identified showing this variant in trans with a pathogenic ATM variant in an individual with ataxia-telangiectasia. Available evidence is insufficient to assign PM3 points. Details ▾Hide ▴
Rule
ATM PM3 uses a point-based framework for recessive disease observations in trans with a pathogenic variant.
Evidence considered
- No phase-qualified recessive case data identified in reviewed materials
Still missing
- No trans-phase data were identified.
- No ATM-related recessive proband evidence meeting the PM3 point framework was identified.
Sources
PP1 No segregation data were identified for this variant in affected relatives, so PP1 cannot be assessed from the available evidence. Details ▾Hide ▴
Rule
ATM PP1 for the recessive condition requires segregation in affected relatives.
Evidence considered
- No segregation evidence identified in reviewed materials
Still missing
- No family segregation data were identified.
Sources
literature_passcspec ↗
BP2 No evidence was identified showing this variant in trans with a pathogenic ATM variant in an unaffected individual or other setting that would qualify for BP2 points. Available evidence is insufficient to assess BP2. Details ▾Hide ▴
Rule
ATM BP2 uses a point-based framework for observations in trans with a pathogenic variant in unaffected individuals/settings.
Evidence considered
- No qualifying BP2 co-occurrence evidence identified in reviewed materials
Still missing
- No qualifying co-occurrence data in unaffected individuals were identified.
- No phase-qualified benign point evidence was identified.
Sources
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant, and available evidence does not place it in the null-variant categories used for ATM PVS1. ATM-specific PVS1 guidance is therefore not applicable. Details ▾Hide ▴
Rule
ATM PVS1 decision tree applies to qualifying loss-of-function variants; this missense variant does not meet those entry criteria.
Evidence considered
- NM_000051.4:c.6059G>T encodes p.(Gly2020Val)
- pvs1_gene_context: ATM is PVS1-eligible at the gene level
- pvs1_variant_assessment: variant_bucket=other, canonical_splice_consensus=false, apply_generic_pvs1_framework=false
Sources
PS2 N/AATM-specific guidance lists PS2 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: PS2 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks PS2 as not applicable
Sources
PM1 N/AATM-specific guidance lists PM1 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: PM1 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks PM1 as not applicable
Sources
PM4 N/AThis is not a stop-loss variant, so PM4 does not apply. Details ▾Hide ▴
Rule
ATM PM4 is used for stop-loss variants.
Evidence considered
- Variant consequence: missense
Sources
prefetchcspec ↗
PM5 N/AATM-specific PM5 guidance applies to truncating or qualifying splice variants upstream of p.Arg3047, not to this missense substitution. PM5 is therefore not applicable. Details ▾Hide ▴
Rule
ATM PM5_Supporting applies to qualifying truncating or splice variants upstream of p.Arg3047.
Evidence considered
- Variant consequence: missense
- ATM CSPEC PM5 description is limited to truncating or qualifying splice variants upstream of p.Arg3047
Sources
prefetchcspec ↗
PM6 N/AATM-specific guidance lists PM6 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: PM6 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks PM6 as not applicable
Sources
PP2 N/AATM-specific guidance lists PP2 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: PP2 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks PP2 as not applicable
Sources
PP4 N/AATM-specific guidance lists PP4 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: PP4 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks PP4 as not applicable
Sources
PP5 N/AATM-specific guidance lists PP5 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: PP5 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks PP5 as not applicable
Sources
BS2 N/AATM-specific guidance lists BS2 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: BS2 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks BS2 as not applicable
Sources
BS4 N/AATM-specific guidance lists BS4 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: BS4 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks BS4 as not applicable
Sources
BP1 N/AATM-specific guidance lists BP1 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: BP1 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks BP1 as not applicable
Sources
BP3 N/AATM-specific guidance lists BP3 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: BP3 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks BP3 as not applicable
Sources
BP5 N/AATM-specific guidance lists BP5 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: BP5 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks BP5 as not applicable
Sources
BP6 N/AATM-specific guidance lists BP6 as not applicable for this framework. Details ▾Hide ▴
Rule
ATM CSPEC/VCEP: BP6 not applicable.
Evidence considered
- ATM CSPEC/VCEP marks BP6 as not applicable
Sources
BP7 N/AThis is a missense variant rather than a synonymous or qualifying deep intronic variant, so BP7 does not apply. Details ▾Hide ▴
Rule
ATM BP7 applies to synonymous and qualifying deep intronic variants, with or without RNA evidence depending on context.
Evidence considered
- Variant consequence: missense
Sources
prefetchcspec ↗
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.6059G>T
- Protein (HGVS p.)
- NP_000042.3:p.(Gly2020Val)
- GRCh38
- chr11:108315875 G>T
- GRCh37
- chr11:108186602 G>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
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 SupportingIn silico evidence supports a deleterious effect for this missense variant because the REVEL score is 0.753, which is above the ATM PP3 threshold of >0.7333. SpliceAI predicts no meaningful splice effect with a max delta score of 0.02, supporting interpretation as a missense change rather than a splice-altering variant. Details ▾Hide ▴
Rule
ATM PP3 for missense variants: REVEL >0.7333.
Evidence considered
- REVEL = 0.753
- SpliceAI max delta score = 0.02
Sources
BP4 Benign computational evidence is not supported because the REVEL score is 0.753, which is above the ATM BP4 missense threshold of ≤0.249. Although SpliceAI is low at 0.02 and does not predict splice disruption, the missense prediction does not support BP4. Details ▾Hide ▴
Rule
ATM BP4 for missense variants: REVEL ≤0.249; for splicing, SpliceAI ≤0.1 supports no splice impact.
Evidence considered
- REVEL = 0.753
- SpliceAI max delta score = 0.02
Sources
BP7 N/AThis is a missense variant rather than a synonymous or qualifying deep intronic variant, so BP7 does not apply. Details ▾Hide ▴
Rule
ATM BP7 applies to synonymous and qualifying deep intronic variants, with or without RNA evidence depending on context.
Evidence considered
- Variant consequence: missense
Sources
prefetchcspec ↗
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
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/955939/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108186602-G-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108315875-G-T?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.6059…
- OncoKB ↗www.oncokb.org/gene/ATM/G2020V
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.6059G%3ET
- 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 Uncertain significance (3 clinical laboratories).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
Functional
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: 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.