About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.7381C>T, p.(Arg2461Cys)
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
ATM VCEP applies BP4_Supporting when SpliceAI predicts no splicing impact (max delta ≤0.1). SpliceAI predicts no significant splice impact for c.7381C>T (max delta score = 0.07), meeting the VCEP BP4 threshold for absence of predicted splicing disruption. The REVEL score of 0.707 does not meet the missense BP4 threshold (≤0.249), but BP4 is independently satisfied by the splicing computational evidence.
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
99 / 1,614,160 alleles
gnomAD v4.1: 99 / 1,614,160 alleles. Recorded AF 6.13322e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.19748e-05; MAF= 0.00920%, 26/282686 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000600625; MAF= 0.06006%, 15/24974 alleles, homozygotes = 0); grpmax FAF= 0.0003336.
No listed criterion applied
SpliceAI score
0.070 maximum delta
Recorded SpliceAI maximum delta score: 0.070. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
19 reported laboratory submissions
14 Uncertain significance · 3 Likely benign · 1 Benign · 1 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.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV53748241, n = 2 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.
26 criteria with recorded statuses: 1 met · 8 not met · 1 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.7381C>T (p.Arg2461Cys) is a missense variant in ATM, a gene where loss of function is an established mechanism for Ataxia-Telangiectasia (AR) and heterozygous variants confer moderate risk for breast and other cancers (AD).
This variant is not a null variant and SpliceAI predicts no splicing impact (max delta 0.07); PVS1 is not applicable per the ATM VCEP v1.5.0 decision tree.
This variant is present in gnomAD v4.1 at an overall allele frequency of 0.00613% (99/1,614,160 alleles; 0 homozygotes) with a grpmax filtering AF of 0.039%. The frequency exceeds the PM2_Supporting threshold (≤0.001%) but does not reach BS1 (>0.05%) or BA1 (>0.5%).
In silico predictions are inconclusive: REVEL score of 0.707 falls between the PP3 threshold (>0.7333) and BP4 missense threshold (≤0.249), neither meeting nor refuting pathogenicity. However, SpliceAI predicts no splicing impact (max delta 0.07 ≤ 0.1), satisfying BP4_Supporting.
This variant has been reported in ClinVar (VCV000142541) with predominantly uncertain significance classifications (14 clinical laboratories), with a minority of likely benign (3) and benign (1) submissions. No expert panel classification is available.
Functional evidence from the VCEP-validated Barone 2009 (PMID:19431188) kinase assay suggests partial impairment of ATM autophosphorylation, potentially supporting PS3_Supporting, but full-text verification of the variant-specific result was not possible in this assessment. Human review is recommended.
No case-control study meeting PS4 criteria, no published segregation data for PP1, and no phased trans/cis data for PM3/BP2 were identified for this variant.
Applying the ATM VCEP v1.5.0 criteria combination rules (Richards et al. 2015), only BP4_Supporting is met with no pathogenic criteria satisfied. The variant is classified as a Variant of Uncertain Significance (VUS). If PS3_Supporting is confirmed upon human review of the functional data, the variant would remain VUS (1 pathogenic supporting + 1 benign supporting under Rule31).
No criteria match.
Met · 1
BP4 SupportingATM VCEP applies BP4_Supporting when SpliceAI predicts no splicing impact (max delta ≤0.1). SpliceAI predicts no significant splice impact for c.7381C>T (max delta score = 0.07), meeting the VCEP BP4 threshold for absence of predicted splicing disruption. The REVEL score of 0.707 does not meet the missense BP4 threshold (≤0.249), but BP4 is independently satisfied by the splicing computational evidence. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.07 ≤ VCEP BP4 threshold of 0.1 — no predicted splicing impact
- REVEL 0.707 does not separately meet BP4 missense threshold of ≤0.249
Sources
Not met · 8 · evaluated, threshold not reached
PS4 ATM VCEP requires a case-control study with p≤0.05 and OR≥2 (or lower 95% CI≥1.5) for PS4_Strong. No published case-control study with statistically significant enrichment of c.7381C>T in affected individuals versus controls was identified. The variant has been observed in cancer cohorts (ClinVar submissions, sarcoma study PMID:27498913) but without formal case-control odds ratio calculation for this specific variant. Details ▾Hide ▴
Evidence considered
- No case-control study meeting VCEP PS4 thresholds identified
- Variant observed in ClinVar across multiple cancer-related submissions without aggregate OR
- gnomAD frequency (0.00613%) is low but population data alone is insufficient for PS4
Still missing
- No published case-control odds ratio for this specific variant
- Aggregate proband counting across published cohorts may exist but was not located
Sources
PM2 ATM VCEP applies PM2_Supporting when frequency is ≤0.001% in gnomAD v4. The variant has a gnomAD v4.1 overall allele frequency of 0.00613% (99/1,614,160 alleles), which exceeds the 0.001% threshold. The highest subpopulation frequency is 0.052% in African/African American (39/75,046 alleles). Although rare, the frequency does not meet the VCEP-defined cutoff for PM2_Supporting. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 0.00613% (99/1
- 614
- 160 alleles) exceeds VCEP PM2 threshold of ≤0.001%
- grpmax FAF v4.1 = 0.039%
- Highest subpopulation AF = 0.052% in African/African American
- 0 homozygotes observed
Sources
PP1 ATM VCEP applies PP1 for AR condition (Ataxia-Telangiectasia) when co-segregation is observed in affected relatives carrying both variants. No published segregation data or co-segregation analysis was identified for c.7381C>T in A-T families. Details ▾Hide ▴
Evidence considered
- No segregation data found in literature or databases for this variant
Still missing
- No published LOD scores or co-segregation analysis in A-T families
- Unpublished segregation data may exist in clinical laboratories
PP3 ATM VCEP applies PP3_Supporting for missense variants when REVEL >0.7333, or for splicing when SpliceAI ≥0.2. The REVEL score for this variant is 0.707, which falls below the 0.7333 threshold. SpliceAI max delta is 0.07, below the 0.2 threshold. Neither computational criterion is met. Details ▾Hide ▴
Evidence considered
- REVEL score 0.707 < VCEP threshold of 0.7333
- SpliceAI max delta 0.07 < VCEP threshold of 0.2
Sources
revelspliceai ↗
BA1 ATM VCEP applies BA1 Stand-Alone when grpmax filtering AF exceeds 0.5% in gnomAD v4. The grpmax FAF for this variant is 0.039% in gnomAD v4.1, well below the 0.5% threshold. This variant is too rare to qualify as a common polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 0.00038979 (0.039%) < VCEP BA1 threshold of >0.5%
Sources
BS1 ATM VCEP applies BS1_Strong when grpmax filtering AF exceeds 0.05% in gnomAD v4. The grpmax FAF for this variant is 0.039% in gnomAD v4.1, below the 0.05% threshold. The variant frequency does not exceed the expected prevalence for ATM-related disorders. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 0.00038979 (0.039%) < VCEP BS1 threshold of >0.05%
Sources
BS3 ATM VCEP applies BS3 when a variant rescues ATM-specific functional features. BS3_Moderate requires rescue of both an ATM-specific feature (e.g., phosphorylation of ATM-specific targets) AND radiosensitivity; BS3_Supporting requires rescue of either. Available evidence from exploratory search suggests p.Arg2461Cys impairs rather than rescues ATM kinase activity. No study demonstrates normal ATM function for this variant. BS3 is not met. Details ▾Hide ▴
Evidence considered
- Functional evidence suggests partial impairment of ATM kinase activity
- not rescue
- VCEP BS3 requires demonstration of normal (rescued) function
BP2 ATM VCEP applies BP2 when a variant is observed in cis with a pathogenic variant for A-T (recessive) or homozygous/trans in an unaffected individual ≥18 years with no evidence of A-T. No phased genotype data demonstrating cis configuration with a known pathogenic ATM variant, and no homozygous or confirmed trans observations in unaffected adults, were identified for c.7381C>T. Details ▾Hide ▴
Evidence considered
- No evidence of cis configuration with a pathogenic ATM variant
- No confirmed trans or homozygous observations in unaffected adults
- gnomAD shows 0 homozygotes
Still missing
- Phasing data unavailable from public databases
- Co-occurrence data may exist in clinical laboratories
Not assessed · 1 · no assessment recorded
PS3 The ATM VCEP functional assay spreadsheet (clingen_hbop_atm_supplementary_tables_1_and_2_v1.xlsx) validates Barone 2009 (PMID:19431188) and Mitui 2009 (PMID:18634022) kinase assays as approved for PS3_Supporting/BS3_Supporting. Exploratory evidence suggests p.Arg2461Cys was tested and showed partial reduction in ATM kinase activity, potentially qualifying for PS3_Supporting under VCEP rules (failure to rescue ATM-specific phosphorylation). However, full-text verification of the specific variant result was not possible — PMID:19431188 and PMID:18634022 full-text files were not available in the case publication set. Human review is needed to confirm variant-specific functional data before applying PS3. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet validates Barone 2009 kinase assay for PS3_Supporting
- Exploratory search reports p.Arg2461Cys showed partial reduction in ATM autophosphorylation
- VCEP rule: PS3_Supporting applies when variant fails to rescue an ATM-specific feature (e.g.
- phosphorylation of ATM-specific targets)
Still missing
- Full-text of PMID:19431188 (Barone 2009) not available for variant-specific result verification
- Full-text of PMID:18634022 (Mitui 2009) not available for variant-specific result verification
- Radiosensitivity assay data needed for potential PS3_Moderate upgrade
Sources
vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies only to null variants (nonsense, frameshift, canonical ±1,2 splice sites) per the ATM VCEP PVS1 decision tree. NM_000051.4:c.7381C>T is a missense variant (p.Arg2461Cys) and SpliceAI predicts no splicing impact (max delta 0.07), so it is not eligible for PVS1. Details ▾Hide ▴
Evidence considered
- Missense variant p.Arg2461Cys is not a null variant
- SpliceAI max delta score 0.07 indicates no predicted splice defect
- ATM VCEP PVS1 decision tree does not apply to missense variants without demonstrated splicing impact
Sources
spliceai ↗vcep_atm_pvs1_1_5
PS1 N/APS1 requires the same amino acid change (Arg2461Cys) resulting from a different nucleotide change. At codon 2461 (CGC→TGC), only c.7381C>T produces p.Arg2461Cys; no alternative nucleotide substitution yields this same amino acid change. No prior P/LP variant with the identical amino acid change exists. Details ▾Hide ▴
Evidence considered
- Only one nucleotide substitution (c.7381C>T) produces p.Arg2461Cys at this codon
Sources
vcep_atm_ps1_1_5
PS2 VCEPATM VCEP v1.5.0 specifies that PS2 is not applicable for AD or AR disease; informative de novo occurrences have not yet been observed for ATM and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PM1 VCEPATM VCEP specifies PM1 is not applicable: 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 ▴
PM5 N/AATM VCEP applies PM5_Supporting only to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, or to splice variants where PVS1_VS(RNA) is applied. This is a missense variant (p.Arg2461Cys), and the VCEP explicitly states: 'Do not use for missense changes: Multiple amino acid substitutions at the same residue can be pathogenic or benign and bioinformatic tools cannot yet confidently distinguish them.' Details ▾Hide ▴
Evidence considered
- Missense variant does not qualify for VCEP PM5 rules
- VCEP explicitly prohibits PM5 for missense changes
Sources
PM6 VCEPATM VCEP v1.5.0 specifies PM6 is not applicable for AD or AR disease; informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PP2 VCEPATM VCEP specifies PP2 is not applicable: ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
PP4 VCEPATM VCEP specifies PP4 is not applicable. For AD: breast cancer is a disease with multiple genetic etiologies and no features distinguish hereditary from sporadic causes. For AR: such evidence is built into the PM3/BP2 table. Details ▾Hide ▴
PP5 VCEPATM VCEP specifies PP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BS2 VCEPATM VCEP specifies BS2 is not applicable: ATM has incomplete penetrance. Details ▾Hide ▴
BS4 VCEPATM VCEP specifies BS4 is not applicable. For AD: co-segregation analysis in low penetrance genes can lead to false positive results. For AR: informative instances of lack of co-segregation in A-T families are too rare to be considered. Details ▾Hide ▴
BP1 VCEPATM VCEP specifies BP1 is not applicable: missense pathogenic variants are known for ATM. Details ▾Hide ▴
BP5 VCEPATM VCEP specifies BP5 is not applicable: cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and ATM has low penetrance resulting in more frequent co-occurrence with other pathogenic variants. Details ▾Hide ▴
BP6 VCEPATM VCEP specifies BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP7 N/AATM VCEP applies BP7 to synonymous and deep intronic variants (further than +7 at donor and -21 at acceptor). c.7381C>T is a missense variant (p.Arg2461Cys), not synonymous. BP7 is not applicable to missense variants. Details ▾Hide ▴
Evidence considered
- Missense variant does not qualify for BP7 which is restricted to synonymous and deep intronic variants
Sources
PS5 N/APS5 is not part of the ATM VCEP v1.5.0 criteria framework. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.7381C>T
- Protein (HGVS p.)
- NP_000042.3:p.(Arg2461Cys)
- GRCh38
- chr11:108330287 C>T
- GRCh37
- chr11:108201014 C>T
- ClinVar
- 142541
- COSMIC
- COSV53748241
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
99 / 1,614,160 alleles
AF 6.13e-05 · 0 homozygotes · FAF 0.00039
gnomAD v2.1
26 / 282,686 alleles
AF 9.2e-05 · 0 homozygotes · FAF 0.000334
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 6.1e-05 · 99 / 1,614,160 alleles · 0 hom · FAF 0.00039
| African/African American39 / 75,046 | 0.00052 |
| South Asian14 / 91,088 | 0.00015 |
| Admixed American4 / 60,018 | 6.7e-05 |
| European (non-Finnish)41 / 1,180,012 | 3.5e-05 |
| Remaining individuals1 / 62,506 | 1.6e-05 |
0 alternate alleles recorded in 5 other groups: European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 9.2e-05 · 26 / 282,686 alleles · 0 hom · FAF 0.00033
| African/African American15 / 24,974 | 0.0006 |
| South Asian7 / 30,616 | 0.00023 |
| Remaining individuals1 / 7,218 | 0.00014 |
| Admixed American1 / 35,436 | 2.8e-05 |
| European (non-Finnish)2 / 129,028 | 1.6e-05 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, East Asian, European (Finnish).
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.13322e-05; MAF= 0.00613%, 99/1614160 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000519681; MAF= 0.05197%, 39/75046 alleles, homozygotes = 0); grpmax FAF= 0.00038979.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.19748e-05; MAF= 0.00920%, 26/282686 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000600625; MAF= 0.06006%, 15/24974 alleles, homozygotes = 0); grpmax FAF= 0.0003336.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.707
- BayesDel
- 0.109
How the predictions were used
BP4 SupportingATM VCEP applies BP4_Supporting when SpliceAI predicts no splicing impact (max delta ≤0.1). SpliceAI predicts no significant splice impact for c.7381C>T (max delta score = 0.07), meeting the VCEP BP4 threshold for absence of predicted splicing disruption. The REVEL score of 0.707 does not meet the missense BP4 threshold (≤0.249), but BP4 is independently satisfied by the splicing computational evidence. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.07 ≤ VCEP BP4 threshold of 0.1 — no predicted splicing impact
- REVEL 0.707 does not separately meet BP4 missense threshold of ≤0.249
Sources
PP3 ATM VCEP applies PP3_Supporting for missense variants when REVEL >0.7333, or for splicing when SpliceAI ≥0.2. The REVEL score for this variant is 0.707, which falls below the 0.7333 threshold. SpliceAI max delta is 0.07, below the 0.2 threshold. Neither computational criterion is met. Details ▾Hide ▴
Evidence considered
- REVEL score 0.707 < VCEP threshold of 0.7333
- SpliceAI max delta 0.07 < VCEP threshold of 0.2
Sources
revelspliceai ↗
BP7 N/AATM VCEP applies BP7 to synonymous and deep intronic variants (further than +7 at donor and -21 at acceptor). c.7381C>T is a missense variant (p.Arg2461Cys), not synonymous. BP7 is not applicable to missense variants. Details ▾Hide ▴
Evidence considered
- Missense variant does not qualify for BP7 which is restricted to synonymous and deep intronic variants
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07). REVEL score = 0.707. BayesDel score = 0.109334.
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 23532176 ↗The ATM signaling network in development and disease.Stracker TH et al. · 2013No paper-specific finding is recorded.
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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 26010451 ↗Amplicon sequencing of colorectal cancer: variant calling in frozen and formalin-fixed samples.Betge J et al. · 2015No paper-specific finding is recorded.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
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PMID 27498913 ↗Monogenic and polygenic determinants of sarcoma risk: an international genetic study.Ballinger ML et al. · 2016No paper-specific finding is recorded.
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PMID 27978560 ↗Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer.Pearlman R et al. · 2017No paper-specific finding is recorded.
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PMID 28135145 ↗Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.Yurgelun MB et al. · 2017No paper-specific finding is recorded.
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PMID 29058119 ↗Comprehensive molecular characterisation of epilepsy-associated glioneuronal tumours.Stone TJ et al. · 2018No 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
99 / 1,614,160 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.070
Open source ↗
ClinVar
14 Uncertain significance · 3 Likely benign · 1 Benign · 1 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/142541/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108201014-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108330287-C-T?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.7381…
- OncoKB ↗www.oncokb.org/gene/ATM/R2461C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122756911
- 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= 6.13322e-05; MAF= 0.00613%, 99/1614160 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000519681; MAF= 0.05197%, 39/75046 alleles, homozygotes = 0); grpmax FAF= 0.00038979.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.19748e-05; MAF= 0.00920%, 26/282686 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000600625; MAF= 0.06006%, 15/24974 alleles, homozygotes = 0); grpmax FAF= 0.0003336.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (14 clinical laboratories) and as Likely benign (3 clinical laboratories) and as Benign (1 clinical laboratory) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 142541)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07). REVEL score = 0.707. BayesDel score = 0.109334.
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; COSV53748241, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.