About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.2689T>A, p.(Phe897Ile)
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
BS3Supporting
BS3 · supporting
Functional assay data from the VCEP supplementary table (PMID 40580951) classifies F897I as 'Functional' with 'Medium-high' confidence, indicating retained ATM kinase activity. Per VCEP HBOP BS3 rules, rescue of an ATM-specific feature (kinase activity) supports BS3_Supporting.
BP4Supporting
BP4 · supporting
REVEL score 0.069 is ≤0.249 (VCEP BP4 missense threshold). SpliceAI max delta score 0.02 is ≤0.1 (VCEP BP4 splicing threshold). Additionally, six in silico protein prediction tools showed no deleterious effect for this variant (PMID 29371908, Fig. 2).
Recorded classification: Likely benign
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: BS3 supporting, 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
57 / 1,613,938 alleles
gnomAD v4.1: 57 / 1,613,938 alleles. Recorded AF 3.53173e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18266e-05; MAF= 0.00318%, 8/251362 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.15731e-05; MAF= 0.00616%, 7/113686 alleles, homozygotes = 0); grpmax FAF= 2.855e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0003256975355553143, 6/18422 alleles, homozygotes = 0).
No listed criterion applied
SpliceAI score
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
16 reported laboratory submissions
16 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.
COSMIC
Cancer Hotspots
Somatic evidence
3 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV99069668, n = 3 times).
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.
29 criteria with recorded statuses: 2 met · 9 not met · 1 not assessed · 17 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.2689T>A (p.Phe897Ile) in ATM is classified as Likely Benign based on two benign supporting criteria: BS3_Supporting (functional assay data demonstrates retained ATM kinase activity) and BP4_Supporting (REVEL 0.069, SpliceAI max delta 0.02, and six in silico predictors show no deleterious effect).
No pathogenic criteria were met. The variant is present in gnomAD v4 at low frequency (AF 3.53×10⁻⁵, 57/1,613,938 alleles) but does not meet PM2_Supporting (threshold ≤0.001%). It has been reported in ClinVar as Uncertain Significance (Variation ID 188232, 16 clinical laboratories).
The variant was observed in one ovarian cancer proband (PMID 29371908) but no segregation data are available. It has been reported in COSMIC (COSV99069668, n=3 somatic observations) but without established oncogenic significance.
No criteria match.
Met · 2
BS3 SupportingFunctional assay data from the VCEP supplementary table (PMID 40580951) classifies F897I as 'Functional' with 'Medium-high' confidence, indicating retained ATM kinase activity. Per VCEP HBOP BS3 rules, rescue of an ATM-specific feature (kinase activity) supports BS3_Supporting. Details ▾Hide ▴
Evidence considered
- VCEP supplementary table classifies F897I as 'Functional' (combined score 0.108
- confidence: Medium-high).
- VCEP-approved kinase assay framework assigns PS3_Supporting/BS3_Supporting strength for single-feature functional readouts.
Still missing
- No radiosensitivity assay data available for this variant
- BS3 cannot be upgraded to Moderate without demonstrating rescue of both kinase activity AND radiosensitivity.
Sources
vcep_suppl_tables1_pmid_40580951vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1
BP4 SupportingREVEL score 0.069 is ≤0.249 (VCEP BP4 missense threshold). SpliceAI max delta score 0.02 is ≤0.1 (VCEP BP4 splicing threshold). Additionally, six in silico protein prediction tools showed no deleterious effect for this variant (PMID 29371908, Fig. 2). Details ▾Hide ▴
Evidence considered
- REVEL: 0.069 ≤ 0.249.
- SpliceAI max delta: 0.02 ≤ 0.1.
- BayesDel: -0.350 (benign prediction).
- PMID 29371908 Fig. 2: none of six protein prediction tools (FATHMM
- PolyPhen2
- MutationTaster
- MutationAssessor
- SIFT
- PROVEAN) showed deleterious effect.
Sources
Not met · 9 · evaluated, threshold not reached
PS1 No pathogenic or likely pathogenic missense variant identified at residue Phe897 to serve as a PS1 comparator. Other substitutions at this position (F897V, F897L, F897Y, F897S, F897C) are classified as VUS or are of uncertain significance in ClinVar and VCEP functional data. Details ▾Hide ▴
Evidence considered
- VCEP supplementary functional table lists five alternative substitutions at Phe897
- none classified as pathogenic or likely pathogenic.
- ClinVar lists NM_000051.4:c.2689T>A as VUS with no expert-panel classification.
Sources
vcep_suppl_tables1_pmid_40580951clinvar ↗
PS3 Functional assay data from the VCEP supplementary table (PMID 40580951) classifies F897I as 'Functional' with 'Medium-high' confidence, indicating retention of ATM kinase activity. The variant does not demonstrate loss of function; PS3 is not met. Details ▾Hide ▴
Evidence considered
- VCEP supplementary functional table classifies F897I as 'Functional' (combined score 0.108
- function score 0.064
- eDA score 15.48)
- indicating preserved ATM kinase activity.
Sources
vcep_suppl_tables1_pmid_40580951
PS4 No case-control study meeting VCEP PS4 thresholds (p≤0.05 AND OR≥2 or lower 95% CI≥1.5) identified for this variant. The variant is rare in population databases (gnomAD v4 AF 3.53×10⁻⁵) but no enrichment in affected cohorts has been demonstrated. Details ▾Hide ▴
Evidence considered
- gnomAD v4: 57/1
- 613
- 938 alleles (AF 3.53×10⁻⁵)
- gnomAD v2.1: 8/251
- 362 alleles (AF 3.18×10⁻⁵).
- No published case-control data meeting VCEP statistical thresholds.
Still missing
- No case-control or cohort enrichment study with adequate statistical power for this rare variant.
Sources
PM2 gnomAD v4 allele frequency is 3.53×10⁻⁵ (0.00353%; 57/1,613,938 alleles), exceeding the VCEP PM2_Supporting threshold of ≤0.001%. Observed in 54 alleles in the European (non-Finnish) subpopulation; not a singleton observation. Details ▾Hide ▴
Evidence considered
- gnomAD v4 overall AF 3.53×10⁻⁵ (0.00353%) > 0.001% threshold.
- European (non-Finnish) subpopulation: 54/1
- 179
- 994 alleles
- far exceeding n=1 singleton exception.
Sources
PP1 No segregation data available. The variant was observed in a single proband with ovarian cancer diagnosed at age 67 (PMID 29371908, patient 17,161, from a BRCA2 c.5217_5223delTTTAAGT family) but no co-segregation analysis in relatives was performed. Details ▾Hide ▴
Evidence considered
- PMID 29371908: variant identified in one ovarian cancer proband
- no family segregation data reported.
Still missing
- No co-segregation analysis in affected or unaffected relatives.
Sources
PP3 REVEL score 0.069 falls below the VCEP PP3 missense threshold of >0.7333. SpliceAI max delta score 0.02 is below the VCEP PP3 splicing threshold of ≥0.2. No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.069 (threshold >0.7333 for PP3).
- SpliceAI max delta: 0.02 (threshold ≥0.2 for PP3).
- BayesDel: -0.350 (negative score
- no deleterious prediction).
Sources
BA1 gnomAD v4 grpmax filtering allele frequency is 3.59×10⁻⁵ (0.00359%), well below the VCEP BA1 threshold of >0.5%. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF: 3.59×10⁻⁵ (0.00359%) << 0.5% BA1 threshold.
Sources
BS1 gnomAD v4 grpmax filtering allele frequency is 3.59×10⁻⁵ (0.00359%), below the VCEP BS1 threshold of >0.05%. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF: 3.59×10⁻⁵ (0.00359%) < 0.05% BS1 threshold.
Sources
BP2 No co-occurrence data in trans with a pathogenic ATM variant in Ataxia Telangiectasia probands is available. The variant has not been observed in homozygous state in population databases (gnomAD homozygotes = 0). Details ▾Hide ▴
Evidence considered
- gnomAD v4: 0 homozygotes.
- No published observations of this variant in trans with a known pathogenic ATM variant in A-T patients.
Still missing
- No trans-phase data in ATM-related recessive disease.
Sources
Not assessed · 1 · no assessment recorded
PS5 No additional source of pathogenic evidence identified beyond what was evaluated under other criteria. No new strong functional or clinical data available. Details ▾Hide ▴
Still missing
- No additional data source identified for PS5 evaluation.
Not applicable · 17· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AMissense substitution (Phe897Ile); PVS1 is reserved for null variants (nonsense, frameshift, canonical ±1,2 splice sites) per VCEP HBOP ATM PVS1 decision tree. Details ▾Hide ▴
No further detail was recorded.
PS2 VCEPVCEP HBOP panel explicitly marks PS2 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
PM1 VCEPVCEP HBOP panel explicitly marks PM1 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
PM3 N/ASkipped: PM3 (in trans with pathogenic variant for recessive disorders) requires observation of the variant in trans with a pathogenic ATM variant in an A-T-affected proband; no such data were collected for this case. Details ▾Hide ▴
No further detail was recorded.
PM4 N/ASkipped: PM4 (protein length change) applies to stop-loss or in-frame deletion/insertion variants; this is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 per VCEP HBOP applies only to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, or to splice variants with NMD-prone PTCs. This is a missense substitution (Phe897Ile). Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPVCEP HBOP panel explicitly marks PM6 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
PP2 VCEPVCEP HBOP panel explicitly marks PP2 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
PP4 VCEPVCEP HBOP panel explicitly marks PP4 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
PP5 VCEPVCEP HBOP panel explicitly marks PP5 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
BS2 VCEPVCEP HBOP panel explicitly marks BS2 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
BS4 VCEPVCEP HBOP panel explicitly marks BS4 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
BP1 VCEPVCEP HBOP panel explicitly marks BP1 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
BP3 VCEPSkipped: BP3 (in-frame deletions/insertions in repetitive regions) applies to in-frame indels in repetitive regions without known function; this is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPVCEP HBOP panel explicitly marks BP5 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
BP6 VCEPVCEP HBOP panel explicitly marks BP6 as Not Applicable for ATM. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 per VCEP applies to synonymous and deep intronic variants. This is a missense substitution (Phe897Ile). BP7(RNA) also applies only to silent substitutions and intronic variants. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.2689T>A
- Protein (HGVS p.)
- NP_000042.3:p.(Phe897Ile)
- GRCh38
- chr11:108268460 T>A
- GRCh37
- chr11:108139187 T>A
- ClinVar
- 188232
- COSMIC
- COSV99069668
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
57 / 1,613,938 alleles
AF 3.53e-05 · 0 homozygotes · FAF 3.58e-05
gnomAD v2.1
8 / 251,362 alleles
AF 3.18e-05 · 0 homozygotes · FAF 2.86e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 3.5e-05 · 57 / 1,613,938 alleles · 0 hom · FAF 3.6e-05
| European (non-Finnish)54 / 1,179,994 | 4.6e-05 |
| Admixed American1 / 59,998 | 1.7e-05 |
| Remaining individuals1 / 62,486 | 1.6e-05 |
| African/African American1 / 74,930 | 1.3e-05 |
0 alternate alleles recorded in 6 other groups: European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 3.2e-05 · 8 / 251,362 alleles · 0 hom · FAF 2.9e-05
| European (non-Finnish)7 / 113,686 | 6.2e-05 |
| Admixed American1 / 34,584 | 2.9e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.53173e-05; MAF= 0.00353%, 57/1613938 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.57629e-05; MAF= 0.00458%, 54/1179994 alleles, homozygotes = 0); grpmax FAF= 3.585e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18266e-05; MAF= 0.00318%, 8/251362 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.15731e-05; MAF= 0.00616%, 7/113686 alleles, homozygotes = 0); grpmax FAF= 2.855e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0003256975355553143, 6/18422 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.069
- BayesDel
- -0.350
How the predictions were used
BP4 SupportingREVEL score 0.069 is ≤0.249 (VCEP BP4 missense threshold). SpliceAI max delta score 0.02 is ≤0.1 (VCEP BP4 splicing threshold). Additionally, six in silico protein prediction tools showed no deleterious effect for this variant (PMID 29371908, Fig. 2). Details ▾Hide ▴
Evidence considered
- REVEL: 0.069 ≤ 0.249.
- SpliceAI max delta: 0.02 ≤ 0.1.
- BayesDel: -0.350 (benign prediction).
- PMID 29371908 Fig. 2: none of six protein prediction tools (FATHMM
- PolyPhen2
- MutationTaster
- MutationAssessor
- SIFT
- PROVEAN) showed deleterious effect.
Sources
PP3 REVEL score 0.069 falls below the VCEP PP3 missense threshold of >0.7333. SpliceAI max delta score 0.02 is below the VCEP PP3 splicing threshold of ≥0.2. No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.069 (threshold >0.7333 for PP3).
- SpliceAI max delta: 0.02 (threshold ≥0.2 for PP3).
- BayesDel: -0.350 (negative score
- no deleterious prediction).
Sources
BP7 N/ABP7 per VCEP applies to synonymous and deep intronic variants. This is a missense substitution (Phe897Ile). BP7(RNA) also applies only to silent substitutions and intronic variants. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.069. BayesDel score = -0.350015.
8 paper records listed. 1 cited in the classification.
Cited in the classification
-
PMID 29371908 ↗Genetic variants of prospectively demonstrated phenocopies in BRCA1/2 kindreds.Dominguez-Valentin M et al. · 2018ATM c.2689T>A (p.Phe897Ile) identified as a variant of unknown significance in a 67-year-old ovarian cancer proband from a BRCA2 c.5217_5223delTTTAAGT family. None of six in silico protein prediction tools (FATHMM, PolyPhen2-HVAR, MutationTaster, MutationAssessor, SIFT, PROVEAN) showed a deleterious effect. The variant had a non-Finnish European ExAC frequency of 4.5×10⁻⁵.→ BP4 Names this variant
Source detail
none of the six prediction tools showed deleterious effects for the detected variants in the AXIN2, ATM, RAD51B and MAP3K1 genes (AXIN2 c.2272G > A, ATM c.2689 T > A, RAD51B c.539A > G and c.1063G > A and MAP3K1 c.764A > G)
Location Table 2 (patient 17,161); Results section (in silico analysis paragraph); Figure 2
Other 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 the interpretation of sequence variants. NM_000051.4:c.2689T>A was not discussed in this publication.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Standardized DNA variant scoring system for pathogenicity assessments in Mendelian disorders. NM_000051.4:c.2689T>A was not discussed in this publication.Does not name this variant
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PMID 28726808 ↗Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.Chaffee KG et al. · 2018Panel-based genetic testing of 25 cancer susceptibility genes in pancreatic ductal adenocarcinoma patients with positive family history identified germline ATM mutations but NM_000051.4:c.2689T>A was not among the variants reported.Does not name this variant
-
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. · 2017Case-control sequencing study of ATM, CHEK2, PALB2, and XRCC2 in 13,087 breast cancer cases and 5,488 controls from East Anglia, UK, focusing on rare protein-truncating variants. NM_000051.4:c.2689T>A was not among the variants reported.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.2689T>A was not discussed in this publication.Does not name this variant
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PMID 34262154 ↗Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.Dalmasso B et al. · 2021Joint analysis of germline ATM variants in 2,104 familial, multiple primary, and sporadic melanoma cases across GenoMEL and MelaNostrum consortia. The study focused on loss-of-function variants and VUS enrichment but NM_000051.4:c.2689T>A was not individually reported or analyzed.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. · 2007National Society of Genetic Counselors practice recommendations for hereditary breast and ovarian cancer risk assessment and genetic counseling. NM_000051.4:c.2689T>A was not discussed in this publication.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
57 / 1,613,938 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.020
Open source ↗
ClinVar
16 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/188232/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108139187-T-A?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108268460-T-A?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108268460-T-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.2689…
- OncoKB ↗www.oncokb.org/gene/ATM/F897I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122712411
- 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= 3.53173e-05; MAF= 0.00353%, 57/1613938 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.57629e-05; MAF= 0.00458%, 54/1179994 alleles, homozygotes = 0); grpmax FAF= 3.585e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18266e-05; MAF= 0.00318%, 8/251362 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.15731e-05; MAF= 0.00616%, 7/113686 alleles, homozygotes = 0); grpmax FAF= 2.855e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0003256975355553143, 6/18422 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (16 clinical laboratories). (ClinVarID = 188232)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.069. BayesDel score = -0.350015.
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 previously been reported in somatic cancers (COSMIC; COSV99069668, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.