About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.8155C>T, p.(Arg2719Cys)
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
BS3Supporting
BS3 · supporting
The ATM VCEP BS3_Supporting rule applies when a variant rescues EITHER an ATM-specific feature OR radiosensitivity. Lee et al. 2025 (PMID:40580951, Cell) performed saturation prime editing of all 27,513 possible ATM SNVs and assessed cell fitness in the presence of olaparib, a PARP inhibitor that creates synthetic lethality with ATM deficiency. NM_000051.4:c.8155C>T (p.Arg2719Cys) was classified as 'Functional' with 'High' confidence, indicating the variant retains ATM activity in the DNA damage response and rescues an ATM-specific function.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework was evaluated deterministically with applied criteria: BS3 supporting benign; 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
20 / 1,611,848 alleles
gnomAD v4.1: 20 / 1,611,848 alleles. Recorded AF 1.24081e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19604e-05; MAF= 0.00120%, 3/250828 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.64625e-05; MAF= 0.00265%, 3/113368 alleles, homozygotes = 0); grpmax FAF= 7.03e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.030 maximum delta
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
14 reported laboratory submissions
14 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
7 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV53736920, n = 7 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: 1 met · 12 not met · 0 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(ATM):c.8155C>T (p.Arg2719Cys) is a missense variant in exon 56 of ATM, a gene in which loss of function is an established mechanism for ataxia-telangiectasia (autosomal recessive) and in which pathogenic variants confer moderate risk for hereditary breast, ovarian, and pancreatic cancer.
This variant is present in gnomAD v4.1 at an overall allele frequency of 1.24e-05 (20/1,611,848 alleles; 0 homozygotes) with a grpmax filtering allele frequency of 9.55e-06. The allele frequency slightly exceeds the ATM VCEP PM2_Supporting threshold of ≤0.001%, and no subpopulation has a singleton observation.
In silico predictors are inconclusive: REVEL score is 0.613 (intermediate, not meeting PP3 threshold of >0.7333 nor BP4 threshold of ≤0.249). BayesDel score is -0.091 (weakly favoring benign). SpliceAI predicts no splicing impact (max delta = 0.03).
A comprehensive functional screen of all ATM SNVs by Lee et al. (2025, PMID:40580951, Cell) using saturation prime editing classified p.Arg2719Cys as 'Functional' with 'High' confidence in a PARP inhibitor (olaparib) fitness assay, indicating the variant retains ATM DNA damage response function. Per ATM VCEP v1.5.0, this supports BS3_Supporting (variant rescues an ATM-specific feature).
This variant has been reported in ClinVar as Uncertain Significance by 14 clinical laboratories (Variation ID: 185832). No expert panel classification is available. Three ClinVar submissions with criterion-level data (Ambry Genetics, Invitae, Color Health) also classify the variant as Uncertain Significance.
This variant has been observed in somatic cancers (COSMIC COSV53736920, n=7), but somatic occurrence does not independently inform germline classification under the ATM VCEP framework.
No evidence was found for: a pathogenic missense variant at the same residue (PS1), case-control enrichment (PS4), compound heterozygosity with a pathogenic variant in an A-T patient (PM3), cosegregation with disease (PP1), or observation in trans with a pathogenic variant in an unaffected individual (BP2).
Applying the ATM VCEP v1.5.0 criteria, BS3_Supporting is the only criterion met. All pathogenic criteria are either not met or not applicable. Under the ACMG/AMP 2015 combining rules (adopted by the VCEP), one supporting benign criterion without any pathogenic criteria results in an overall classification of Uncertain Significance.
No criteria match.
Met · 1
BS3 SupportingThe ATM VCEP BS3_Supporting rule applies when a variant rescues EITHER an ATM-specific feature OR radiosensitivity. Lee et al. 2025 (PMID:40580951, Cell) performed saturation prime editing of all 27,513 possible ATM SNVs and assessed cell fitness in the presence of olaparib, a PARP inhibitor that creates synthetic lethality with ATM deficiency. NM_000051.4:c.8155C>T (p.Arg2719Cys) was classified as 'Functional' with 'High' confidence, indicating the variant retains ATM activity in the DNA damage response and rescues an ATM-specific function. Details ▾Hide ▴
Evidence considered
- Lee et al. 2025 (Cell
- Suppl Table S1): R2719C classified as Functional (High confidence) in prime editing PARPi fitness screen
- indicating rescue of ATM-specific DNA damage response function
Sources
Not met · 12 · evaluated, threshold not reached
PS1 No established pathogenic or likely pathogenic missense variant at the same amino acid residue (Arg2719) was identified. The ATM VCEP PS1 rules require a reference (likely) pathogenic variant at the same nucleotide or same donor/acceptor motif for splicing variants. No qualifying comparator variant was found at this residue. Details ▾Hide ▴
Evidence considered
- No pathogenic/likely pathogenic missense variant identified at Arg2719
Still missing
- Comprehensive search for same-residue pathogenic missense variants in ClinVar and literature not exhaustively performed
- low residual uncertainty
PS3 The ATM VCEP PS3 rules require a variant to fail to rescue ATM-specific function(s). Published functional data from Lee et al. 2025 (PMID:40580951; prime editing screen of all ATM SNVs) classified p.Arg2719Cys as 'Functional' with 'High' confidence, indicating retention of ATM activity rather than loss of function. This evidence supports benign effect (BS3), not pathogenic effect. Details ▾Hide ▴
Evidence considered
- Lee et al. 2025 (Cell): R2719C classified as Functional (High confidence) in prime editing PARPi fitness assay — retains ATM function
- does not support PS3
Sources
PMID:40580951 ↗40580951
PS4 The ATM VCEP PS4 rule requires case-control studies with p-value ≤0.05 and OR ≥2 (or lower 95% CI ≥1.5). No case-control study specifically evaluating NM_000051.4:c.8155C>T was identified. The available literature (PMID:28779002, PMID:33471991) examined ATM truncating variants, not this specific missense variant, and did not provide variant-level case-control data for c.8155C>T. Details ▾Hide ▴
Evidence considered
- No variant-specific case-control study with OR/p-value identified
Still missing
- No systematic case-control analysis for this specific missense variant
Sources
2877900233471991
PM2 The ATM VCEP PM2_Supporting rule requires allele frequency ≤0.001% in gnomAD v4. This variant has an allele frequency of 1.24e-05 (0.00124%, 20/1,611,848 alleles) in gnomAD v4.1, which slightly exceeds the ≤0.001% threshold. No single subpopulation has n=1 (lowest subpopulation count is n=2 in South Asian population), so the n=1 exception does not apply. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: AF=1.24e-05 (0.00124%)
- 20/1
- 611
- 848 alleles
- 0 homozygotes
- grpmax FAF=9.55e-06
- AF exceeds 0.001% threshold
Sources
PM3 The ATM VCEP PM3 rule requires observation of the variant in trans with a pathogenic variant in probands with ataxia-telangiectasia (A-T). No published case or database entry was identified showing NM_000051.4:c.8155C>T in trans with a known pathogenic ATM variant in an A-T patient. Exploratory search of LOVD and PubMed did not yield qualifying compound heterozygote records. Details ▾Hide ▴
Evidence considered
- No A-T proband identified with this variant in trans with a pathogenic ATM variant
Still missing
- No compound heterozygote records found in LOVD or literature for this variant
PP1 The ATM VCEP PP1 rule requires cosegregation with disease in families with ataxia-telangiectasia (AR condition: 1 affected relative = supporting, 2 = moderate, ≥3 = strong). No published family study or segregation data involving NM_000051.4:c.8155C>T was identified. Details ▾Hide ▴
Evidence considered
- No cosegregation data identified for this variant
Still missing
- No family studies with variant segregation data available
PP3 The ATM VCEP PP3 rule for missense variants requires REVEL >0.7333. The REVEL score for this variant is 0.613, which does not meet the threshold. For splicing prediction, PP3 requires SpliceAI ≥0.2; the SpliceAI max delta score is 0.03, which also does not meet the threshold. Details ▾Hide ▴
Evidence considered
- REVEL=0.613 (threshold >0.7333 not met)
- SpliceAI max delta=0.03 (threshold ≥0.2 not met)
- BayesDel=-0.091 (supports benign prediction)
Sources
revelspliceai ↗
BA1 The ATM VCEP BA1 rule requires a grpmax filtering allele frequency >0.5% in gnomAD v4. The grpmax FAF for this variant is 9.55e-06 (0.000955%), far below the 0.5% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=9.55e-06
- well below BA1 threshold of >0.5%
Sources
BS1 The ATM VCEP BS1 rule requires a grpmax filtering allele frequency >0.05% in gnomAD v4. The grpmax FAF for this variant is 9.55e-06 (0.000955%), far below the 0.05% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=9.55e-06
- well below BS1 threshold of >0.05%
Sources
BP2 The ATM VCEP BP2 rule assigns points when the variant is observed in trans with a pathogenic or likely pathogenic ATM variant in an unaffected (non-A-T) individual. No such observation was identified in the available evidence. The exploratory search did not find any unaffected individuals carrying this variant in trans with a pathogenic ATM variant. Details ▾Hide ▴
Evidence considered
- No unaffected individual identified with this variant in trans with pathogenic ATM variant
Still missing
- No trans observations in unaffected individuals identified
BP4 The ATM VCEP BP4 rule for missense variants requires REVEL ≤0.249. The REVEL score for this variant is 0.613, which does not meet the benign threshold. Although SpliceAI predicts no splicing impact (max delta=0.03 ≤0.1), the missense-specific REVEL rule takes precedence and is not satisfied. Details ▾Hide ▴
Evidence considered
- REVEL=0.613 (threshold ≤0.249 not met)
- SpliceAI max delta=0.03 (no splicing impact predicted)
- BayesDel=-0.091 (supports benign)
Sources
revelspliceai ↗
BP7 The ATM VCEP BP7 rule applies to synonymous and deep intronic variants (further than +7 and -21 from donor/acceptor sites). The BP7(RNA) sub-rule can apply when RNA studies demonstrate a lack of aberrant splicing for silent or intronic variants. NM_000051.4:c.8155C>T is a missense variant, not a synonymous or deep intronic variant, and therefore does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 applies to synonymous/deep intronic variants only. SpliceAI max delta=0.03 confirms no splicing impact
- but variant class does not match BP7 criteria
Sources
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is applicable to null variants (nonsense, frameshift, canonical splice, initiation codon, exon deletion). NM_000051.4:c.8155C>T is a missense variant (p.Arg2719Cys) and does not fall into any PVS1 null-variant bucket under the ATM VCEP v1.5.0 PVS1 decision tree. Details ▾Hide ▴
Evidence considered
- Missense variant
- PVS1 only applicable to null variants per ATM VCEP PVS1 decision tree
Sources
vcep_atm_pvs1_1_5
PS2 VCEPPS2 (de novo) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
PM1 VCEPPM1 (mutational hot spot or critical functional domain) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
PM4 N/APM4 (protein length changes due to in-frame deletions/insertions or stop-loss) is restricted to stop-loss variants by the ATM VCEP v1.5.0. This is a missense variant and does not qualify. Details ▾Hide ▴
Evidence considered
- VCEP PM4 restricted to stop-loss variants
- missense variant does not qualify
Sources
PM5 N/AThe ATM VCEP PM5 rule is a truncation-cutoff criterion applied to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, or splice variants with NMD-prone PTCs upstream of p.Arg3047. This missense variant does not create a premature termination codon and is not eligible for PM5 under VCEP specifications. Details ▾Hide ▴
Evidence considered
- VCEP PM5 is a truncation-cutoff rule
- missense variant does not qualify
Sources
PM6 VCEPPM6 (assumed de novo) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
PP2 VCEPPP2 (missense in gene with low rate of benign missense) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
PP4 VCEPPP4 (patient phenotype or family history highly specific for gene) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
PP5 VCEPPP5 (reputable source reports variant as pathogenic) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
BS2 VCEPBS2 (observed in healthy adult with full penetrance expected) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
BS4 VCEPBS4 (lack of segregation) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
BP1 VCEPBP1 (missense in gene where truncating cause disease) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
BP3 VCEPBP3 (in-frame indels in repetitive region) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
BP5 VCEPBP5 (variant found in case with alternate molecular basis) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
BP6 VCEPBP6 (reputable source reports variant as benign) is marked Not Applicable by the ATM VCEP v1.5.0 specifications. Details ▾Hide ▴
PS5 N/APS5 (same residue as pathogenic variant but different nucleotide change leading to different amino acid) is not defined in the ATM VCEP v1.5.0 criteria; PM5 replaces this criterion in the VCEP specification with a truncation-cutoff rule not applicable to missense variants. Generic PS5 is not assessed because the VCEP framework takes precedence. Details ▾Hide ▴
Evidence considered
- PS5 superseded by VCEP PM5 truncation-cutoff rule
- not independently assessed
Sources
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.8155C>T
- Protein (HGVS p.)
- NP_000042.3:p.(Arg2719Cys)
- GRCh38
- chr11:108335848 C>T
- GRCh37
- chr11:108206575 C>T
- ClinVar
- 185832
- COSMIC
- COSV53736920
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
20 / 1,611,848 alleles
AF 1.24e-05 · 0 homozygotes · FAF 9.55e-06
gnomAD v2.1
3 / 250,828 alleles
AF 1.2e-05 · 0 homozygotes · FAF 7.03e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.2e-05 · 20 / 1,611,848 alleles · 0 hom · FAF 9.6e-06
| South Asian2 / 91,006 | 2.2e-05 |
| European (non-Finnish)18 / 1,178,322 | 1.5e-05 |
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 1.2e-05 · 3 / 250,828 alleles · 0 hom · FAF 7e-06
| European (non-Finnish)3 / 113,368 | 2.6e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.24081e-05; MAF= 0.00124%, 20/1611848 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.19766e-05; MAF= 0.00220%, 2/91006 alleles, homozygotes = 0); grpmax FAF= 9.55e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19604e-05; MAF= 0.00120%, 3/250828 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.64625e-05; MAF= 0.00265%, 3/113368 alleles, homozygotes = 0); grpmax FAF= 7.03e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.613
- BayesDel
- -0.091
How the predictions were used
PP3 The ATM VCEP PP3 rule for missense variants requires REVEL >0.7333. The REVEL score for this variant is 0.613, which does not meet the threshold. For splicing prediction, PP3 requires SpliceAI ≥0.2; the SpliceAI max delta score is 0.03, which also does not meet the threshold. Details ▾Hide ▴
Evidence considered
- REVEL=0.613 (threshold >0.7333 not met)
- SpliceAI max delta=0.03 (threshold ≥0.2 not met)
- BayesDel=-0.091 (supports benign prediction)
Sources
revelspliceai ↗
BP4 The ATM VCEP BP4 rule for missense variants requires REVEL ≤0.249. The REVEL score for this variant is 0.613, which does not meet the benign threshold. Although SpliceAI predicts no splicing impact (max delta=0.03 ≤0.1), the missense-specific REVEL rule takes precedence and is not satisfied. Details ▾Hide ▴
Evidence considered
- REVEL=0.613 (threshold ≤0.249 not met)
- SpliceAI max delta=0.03 (no splicing impact predicted)
- BayesDel=-0.091 (supports benign)
Sources
revelspliceai ↗
BP7 The ATM VCEP BP7 rule applies to synonymous and deep intronic variants (further than +7 and -21 from donor/acceptor sites). The BP7(RNA) sub-rule can apply when RNA studies demonstrate a lack of aberrant splicing for silent or intronic variants. NM_000051.4:c.8155C>T is a missense variant, not a synonymous or deep intronic variant, and therefore does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 applies to synonymous/deep intronic variants only. SpliceAI max delta=0.03 confirms no splicing impact
- but variant class does not match BP7 criteria
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.613. BayesDel score = -0.0911133.
9 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
-
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.
-
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. · 2017No paper-specific finding is recorded.
-
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.No paper-specific finding is recorded.
-
PMID 40580951 ↗Functional assessment of all ATM SNVs using prime editing and deep learning.Lee KS et al. · 2025No paper-specific finding is recorded.
-
PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
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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. · 2007No paper-specific finding is recorded.
-
PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008No paper-specific finding is recorded.
-
PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993No 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
20 / 1,611,848 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.030
Open source ↗
ClinVar
14 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/185832/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108206575-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108335848-C-T?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108335848-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.8155…
- OncoKB ↗www.oncokb.org/gene/ATM/R2719C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122703399
- 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= 1.24081e-05; MAF= 0.00124%, 20/1611848 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.19766e-05; MAF= 0.00220%, 2/91006 alleles, homozygotes = 0); grpmax FAF= 9.55e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19604e-05; MAF= 0.00120%, 3/250828 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.64625e-05; MAF= 0.00265%, 3/113368 alleles, homozygotes = 0); grpmax FAF= 7.03e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (14 clinical laboratories). (ClinVarID = 185832)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.613. BayesDel score = -0.0911133.
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; COSV53736920, n = 7 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.