About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.4574T>C, p.(Ile1525Thr)
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: 0
Benign evidence criteria: 1
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
The VCEP HBOP v1.5.0 BP4 rule for missense variants requires REVEL score ≤0.249. The REVEL score for c.4574T>C is 0.116, which is below the 0.249 threshold. Additionally, SpliceAI predicts no splicing impact (max delta = 0.06, ≤0.1). Multiple lines of in silico evidence suggest no damaging effect on the gene product.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework was evaluated deterministically with applied criteria: BP4 supporting; no rule matched the adjudicated criteria.
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
10 / 1,614,116 alleles
gnomAD v4.1: 10 / 1,614,116 alleles. Recorded AF 6.19534e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95646e-06; MAF= 0.00080%, 2/251368 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 6.53253e-05; MAF= 0.00653%, 2/30616 alleles, homozygotes = 0); grpmax FAF= 1.082e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.060 maximum delta
Recorded SpliceAI maximum delta score: 0.060. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
5 reported laboratory submissions
5 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
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.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
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: 1 met · 11 not met · 0 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.4574T>C (p.Ile1525Thr) is a rare missense variant in ATM, present at extremely low frequency in gnomAD v4.1 (10/1,614,116 alleles; grpmax FAF = 1.425×10⁻⁵).
This variant has been reported in ClinVar as Uncertain Significance by 5 clinical laboratories (ClinVar ID 230535); no expert panel submission is available.
The VCEP HBOP v1.5.0 PVS1 criterion is not applicable because this is a missense variant, not a null variant.
Multiple lines of in silico evidence support a benign impact: REVEL score 0.116 is below the VCEP BP4 threshold (≤0.249), SpliceAI predicts no splice impact (max delta 0.06), and BayesDel score is −0.336. BP4 (supporting benign) is met.
No variant-specific functional studies, case-control data, segregation data, or pathogenic comparator at the same residue were identified in the literature. All other applicable VCEP criteria are not met.
Based on the VCEP HBOP v1.5.0 framework, the only criterion met is BP4_Supporting (benign). No pathogenic criteria are met. With only one supporting benign criterion and no conflicting evidence, the variant does not reach a classification threshold under the ACMG/AMP combining rules and remains a Variant of Uncertain Significance.
No criteria match.
Met · 1
BP4 SupportingThe VCEP HBOP v1.5.0 BP4 rule for missense variants requires REVEL score ≤0.249. The REVEL score for c.4574T>C is 0.116, which is below the 0.249 threshold. Additionally, SpliceAI predicts no splicing impact (max delta = 0.06, ≤0.1). Multiple lines of in silico evidence suggest no damaging effect on the gene product. Details ▾Hide ▴
Evidence considered
- REVEL = 0.116 (≤0.249 threshold met). SpliceAI max delta = 0.06 (≤0.1 threshold met). BayesDel = −0.336 (benign direction). VCEP Suppl Table S1 classifies as 'Functional'.
Sources
Not met · 11 · evaluated, threshold not reached
PS1 No known pathogenic missense variant has been established at codon 1525 of ATM. Per the VCEP HBOP v1.5.0 PS1 rule, this criterion requires a previously established pathogenic variant at the same amino acid residue, with splicing ruled out for both variants. The ClinVar classification for this variant is Uncertain Significance; no pathogenic comparator at Ile1525 exists. Details ▾Hide ▴
Evidence considered
- ClinVar ID 230535: Uncertain Significance. No pathogenic missense comparator at codon 1525 in VCEP curated data.
Sources
clinvar ↗vcep_atm_ps1_1_5
PS3 No variant-specific experimental functional data exists for p.Ile1525Thr. The VCEP HBOP v1.5.0 requires demonstration that the variant fails to rescue an ATM-specific feature (e.g. phosphorylation of ATM-specific targets) for PS3_Supporting, or both an ATM-specific feature and radiosensitivity for PS3_Moderate. The VCEP functional classification table (Suppl_TableS1) classifies c.4574T>C as 'Functional' based on in silico prediction, not experimental evidence. No functional study of this variant was identified in the literature. Details ▾Hide ▴
Evidence considered
- VCEP Suppl Table S1: c.4574T>C classified as 'Functional' (in silico prediction
- combined score = 0.045). No experimental functional study identified.
Still missing
- No experimental functional studies of p.Ile1525Thr in the literature.
Sources
cspec ↗vcep_suppl_tables1_pmid_40580951
PS4 The VCEP HBOP v1.5.0 requires case-control studies demonstrating a statistically significant increase in variant prevalence in affected individuals (p≤0.05 AND OR≥2 or lower 95% CI≥1.5). No such case-control study has been reported for c.4574T>C. The variant is observed at extremely low frequency in gnomAD (AF ~6.2×10⁻⁶) and is classified as Uncertain Significance in ClinVar. Details ▾Hide ▴
Evidence considered
- No case-control data for this variant. ClinVar: VUS (5 submitters). gnomAD v4: 10/1
- 614
- 116 alleles.
Still missing
- No case-control study available.
Sources
PM2 The VCEP HBOP v1.5.0 requires gnomAD v4 grpmax filtering allele frequency ≤0.001% for PM2_Supporting. The observed grpmax FAF is 1.425×10⁻⁵ (0.001425%), which exceeds the VCEP threshold of 0.001%. Although the variant is very rare (10/1,614,116 alleles in gnomAD v4), it does not meet the strict VCEP cutoff, and it is observed in multiple sub-populations (not n=1 in a single sub-population). Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF = 1.425×10⁻⁵ (0.001425%) > VCEP threshold of 0.001%. Total AC=10
- not n=1 in single sub-population.
Sources
PP1 The VCEP HBOP v1.5.0 requires segregation data in affected relatives for the autosomal recessive condition (Ataxia-Telangiectasia). No segregation data for c.4574T>C has been identified in the literature or provided with this case. Details ▾Hide ▴
Evidence considered
- No segregation data available for this variant.
Still missing
- No family segregation studies identified.
Sources
PP3 The VCEP HBOP v1.5.0 requires REVEL score >0.7333 for missense variants. The REVEL score for c.4574T>C is 0.116, well below the pathogenic prediction threshold. SpliceAI max delta score is 0.06, indicating no predicted splicing impact. Details ▾Hide ▴
Evidence considered
- REVEL = 0.116 (threshold >0.7333). SpliceAI max delta = 0.06 (threshold ≥0.2 for splicing). Neither threshold met.
Sources
BA1 The VCEP HBOP v1.5.0 requires grpmax filtering allele frequency >0.5% in gnomAD v4 for BA1 Stand-Alone. The observed grpmax FAF is 1.425×10⁻⁵ (0.001425%), far below the 0.5% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF = 1.425×10⁻⁵ (0.001425%) << 0.5% threshold.
Sources
BS1 The VCEP HBOP v1.5.0 requires grpmax filtering allele frequency >0.05% in gnomAD v4 for BS1. The observed grpmax FAF is 1.425×10⁻⁵ (0.001425%), below the 0.05% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF = 1.425×10⁻⁵ (0.001425%) << 0.05% threshold.
Sources
BS3 The VCEP HBOP v1.5.0 requires experimental functional evidence that the variant rescues ATM-specific features (e.g. phosphorylation of ATM-specific targets) and/or radiosensitivity. No such experimental functional data exists for p.Ile1525Thr in the literature. Details ▾Hide ▴
Evidence considered
- No experimental functional rescue data available for this variant.
Still missing
- No experimental functional rescue studies for p.Ile1525Thr.
Sources
BP2 The VCEP HBOP v1.5.0 BP2 rule requires observation of the variant in trans with a pathogenic variant in an unaffected individual ≥18 years old, or homozygous in an unaffected individual, applying the PM3/BP2 point table. No such observations have been identified for c.4574T>C. Details ▾Hide ▴
Evidence considered
- No evidence of co-occurrence in trans with a pathogenic ATM variant in unaffected individuals.
Still missing
- No trans-phase or homozygous observations in unaffected individuals.
Sources
cspec ↗vcep_atm_pm3_bp2_1_5
PS5 No pathogenic missense variant has been established at codon 1525 of ATM. PS5 (generic ACMG) requires a different pathogenic missense change at the same residue, which is not available for p.Ile1525. The VCEP does not include a PS5 criterion. Details ▾Hide ▴
Evidence considered
- No pathogenic variant at codon 1525.
Sources
clinvar ↗vcep_suppl_tables1_pmid_40580951
Not applicable · 17· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000051.4:c.4574T>C is a missense variant (p.Ile1525Thr). The VCEP PVS1 decision tree applies only to null variants (nonsense, frameshift, canonical ±1,2 splice sites). This variant does not fall into any PVS1 bucket. Details ▾Hide ▴
Evidence considered
- Missense substitution at codon 1525
- not a null variant.
Sources
pvs1_gene_contextpvs1_variant_assessment
PS2 VCEPThe VCEP HBOP v1.5.0 specifies PS2 is not applicable for ATM: informative de novo occurrences have not been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PM1 VCEPThe VCEP HBOP v1.5.0 specifies PM1 is not applicable for ATM: 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 ▴
PM3 N/ATrivially not applicable: no trans-phase or homozygous observations of this variant with a second pathogenic ATM allele in an Ataxia-Telangiectasia proband. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AProtein length changes due to in-frame deletions/insertions or stop-loss; not applicable to this missense substitution. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AThe VCEP HBOP v1.5.0 PM5 rule applies only to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, or to splice variants with NMD-prone PTCs. Missense changes are explicitly excluded: 'Do not use for missense changes.' c.4574T>C is a missense variant (p.Ile1525Thr). Details ▾Hide ▴
Evidence considered
- VCEP PM5 rule: not applicable to missense variants. PM5 candidates analysis confirms truncation-cutoff mode
- not classic same-residue PM5.
Sources
cspec ↗pm5_candidates
PM6 VCEPThe VCEP HBOP v1.5.0 specifies PM6 is not applicable for ATM: informative de novo occurrences have not been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PP2 VCEPThe VCEP HBOP v1.5.0 specifies PP2 is not applicable: ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
PP4 VCEPThe VCEP HBOP v1.5.0 specifies PP4 is not applicable: breast cancer has multiple genetic etiologies (genetic heterogeneity), and for the autosomal recessive condition, such evidence is built into the PM3/BP2 table. Details ▾Hide ▴
PP5 VCEPThe VCEP HBOP v1.5.0 specifies PP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BS2 VCEPThe VCEP HBOP v1.5.0 specifies BS2 is not applicable: ATM has incomplete penetrance. Details ▾Hide ▴
BS4 VCEPThe VCEP HBOP v1.5.0 specifies BS4 is not applicable: lack of co-segregation in A-T families is too rare to be informative, and co-segregation analysis in low-penetrance genes can lead to false positives. Details ▾Hide ▴
BP1 VCEPThe VCEP HBOP v1.5.0 specifies BP1 is not applicable: missense pathogenic variants are known for ATM. Details ▾Hide ▴
Evidence considered
- VCEP rule: not applicable
- missense pathogenic variants exist in ATM.
Sources
BP3 VCEPIn-frame deletions/insertions in repetitive region without known function; not applicable to this missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPThe VCEP HBOP v1.5.0 specifies BP5 is not applicable: cases with multiple pathogenic variants have been observed in breast cancer genes, and ATM has low penetrance with higher tolerance in the general population. Details ▾Hide ▴
BP6 VCEPThe VCEP HBOP v1.5.0 specifies BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP7 N/ANM_000051.4:c.4574T>C is a missense variant (p.Ile1525Thr). The VCEP HBOP v1.5.0 BP7 rule applies only to synonymous and deep intronic variants. Missense variants are not eligible for BP7. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.4574T>C
- Protein (HGVS p.)
- NP_000042.3:p.(Ile1525Thr)
- GRCh38
- chr11:108292756 T>C
- GRCh37
- chr11:108163483 T>C
- ClinVar
- 230535
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
10 / 1,614,116 alleles
AF 6.2e-06 · 0 homozygotes · FAF 1.43e-05
gnomAD v2.1
2 / 251,368 alleles
AF 7.96e-06 · 0 homozygotes · FAF 1.08e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.2e-06 · 10 / 1,614,116 alleles · 0 hom · FAF 1.4e-05
| South Asian4 / 91,084 | 4.4e-05 |
| European (non-Finnish)6 / 1,179,970 | 5.1e-06 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 8e-06 · 2 / 251,368 alleles · 0 hom · FAF 1.1e-05
| South Asian2 / 30,616 | 6.5e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.19534e-06; MAF= 0.00062%, 10/1614116 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 4.39155e-05; MAF= 0.00439%, 4/91084 alleles, homozygotes = 0); grpmax FAF= 1.425e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95646e-06; MAF= 0.00080%, 2/251368 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 6.53253e-05; MAF= 0.00653%, 2/30616 alleles, homozygotes = 0); grpmax FAF= 1.082e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.116
- BayesDel
- -0.336
How the predictions were used
BP4 SupportingThe VCEP HBOP v1.5.0 BP4 rule for missense variants requires REVEL score ≤0.249. The REVEL score for c.4574T>C is 0.116, which is below the 0.249 threshold. Additionally, SpliceAI predicts no splicing impact (max delta = 0.06, ≤0.1). Multiple lines of in silico evidence suggest no damaging effect on the gene product. Details ▾Hide ▴
Evidence considered
- REVEL = 0.116 (≤0.249 threshold met). SpliceAI max delta = 0.06 (≤0.1 threshold met). BayesDel = −0.336 (benign direction). VCEP Suppl Table S1 classifies as 'Functional'.
Sources
PP3 The VCEP HBOP v1.5.0 requires REVEL score >0.7333 for missense variants. The REVEL score for c.4574T>C is 0.116, well below the pathogenic prediction threshold. SpliceAI max delta score is 0.06, indicating no predicted splicing impact. Details ▾Hide ▴
Evidence considered
- REVEL = 0.116 (threshold >0.7333). SpliceAI max delta = 0.06 (threshold ≥0.2 for splicing). Neither threshold met.
Sources
BP7 N/ANM_000051.4:c.4574T>C is a missense variant (p.Ile1525Thr). The VCEP HBOP v1.5.0 BP7 rule applies only to synonymous and deep intronic variants. Missense variants are not eligible for BP7. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06). REVEL score = 0.116. BayesDel score = -0.335733.
8 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 16832357 ↗ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles.Renwick A et al. · 2006Case-control mutation screening of ATM in 443 familial breast cancer pedigrees and 521 controls. Identified 12 truncating/splicing ATM mutations associated with breast cancer risk (OR 2.37). Rare missense variants were catalogued but c.4574T>C (p.Ile1525Thr) was not reported among them.Does not name this variant
Quoted passage
We also identified 37 different missense variants (Supplementary Table 2 online).
Table 1 (truncating mutations); Supplementary Table 2 (missense variants)
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PMID 19781682 ↗Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer.Tavtigian SV et al. · 2009Pooled meta-analysis of seven ATM case-control mutation-screening studies (1544 cases, 1224 controls) plus 987 cases and 1021 controls. Assessed contribution of rare missense substitutions to breast cancer risk using Align-GVGD and SIFT. c.4574T>C (p.Ile1525Thr) was not among the individually reported missense variants.Does not name this variant
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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 sequence variant interpretation. Provides the generic classification framework and combining rules. Does not contain variant-specific data for ATM c.4574T>C.Does not name this variant
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PMID 20301317 ↗Hereditary Ataxia Overview.Adam MP et al. · 1993GeneReviews overview of hereditary ataxia. General clinical description of ataxia-telangiectasia and other hereditary ataxias. No variant-specific data for ATM c.4574T>C.Does not name this variant
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PMID 24366376 ↗Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.USPSTF recommendation statement on BRCA-related cancer risk assessment, genetic counseling, and genetic testing. Focuses on BRCA1/BRCA2, not ATM. No mention of ATM c.4574T>C.Does not name this variant
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. General clinical guidance document with no variant-specific data for ATM c.4574T>C.Does not name this variant
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional VersiPDQ cancer genetics risk assessment and counseling summary. General clinical reference with no variant-specific data for ATM c.4574T>C.Does not name this variant
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PMID 20050888 ↗EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.Gasser T et al. · 2010EFNS guidelines on molecular diagnosis of ataxias and spastic paraplegias. General diagnostic guideline; does not mention ATM c.4574T>C.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
10 / 1,614,116 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.060
Open source ↗
ClinVar
5 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/230535/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108163483-T-C?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108292756-T-C?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108292756-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.4574…
- OncoKB ↗www.oncokb.org/gene/ATM/I1525T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.4574T%3EC
- 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= 6.19534e-06; MAF= 0.00062%, 10/1614116 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 4.39155e-05; MAF= 0.00439%, 4/91084 alleles, homozygotes = 0); grpmax FAF= 1.425e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95646e-06; MAF= 0.00080%, 2/251368 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 6.53253e-05; MAF= 0.00653%, 2/30616 alleles, homozygotes = 0); grpmax FAF= 1.082e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories). (ClinVarID = 230535)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06). REVEL score = 0.116. BayesDel score = -0.335733.
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.