About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.8261C>T, p.(Thr2754Ile)
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: 1
Benign evidence criteria: 0
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is present at extremely low frequency in gnomAD v4.1 (total AF=2.49e-06; 4/1,605,254 alleles; grpmax FAF=2.8e-07; 0 homozygotes), meeting the ATM VCEP PM2_Supporting threshold of ≤0.001% (≤0.00001) in the gnomAD v4 dataset.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework was evaluated deterministically with applied criteria: PM2 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
4 / 1,605,254 alleles
gnomAD v4.1: 4 / 1,605,254 alleles. Recorded AF 2.49182e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18959e-05; MAF= 0.00319%, 1/31352 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.48677e-05; MAF= 0.00649%, 1/15416 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
6 reported laboratory submissions
6 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
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 · 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:c.8261C>T (p.Thr2754Ile) is a missense variant in ATM, a gene for which loss of function is an established mechanism of disease in ataxia-telangiectasia and in which germline variants confer susceptibility to breast, ovarian, and pancreatic cancer (ClinGen HBOP VCEP v1.5.0).
This variant is present at extremely low frequency in population databases: gnomAD v4.1 reports 4 heterozygous carriers among 1,605,254 alleles (total AF=2.49e-06; grpmax FAF=2.8e-07) with no homozygotes observed, and gnomAD v2.1 reports 1 heterozygous carrier among 31,352 alleles (AF=3.19e-05). It is absent from gnomAD-Canada v1.0.
In silico predictors are inconclusive: REVEL score is 0.633 (below the ATM VCEP PP3 threshold of >0.7333 but above the BP4 threshold of ≤0.249), BayesDel score is -0.0763065, and SpliceAI predicts no significant splice impact (max delta score = 0.01).
This variant has been reported in ClinVar as Uncertain Significance by 6 clinical laboratories (ClinVar Variation ID: 127457), with no expert panel classifications available. No functional studies, case-control analyses, segregation data, or observations in trans with pathogenic ATM variants have been identified for this specific variant.
The variant is absent from COSMIC (no somatic cancer reports) and does not fall within a statistically significant Cancer Hotspot. OncoKB reports no reviewed functional evidence and classifies this variant as having Unknown Oncogenic Effect.
Under the ClinGen HBOP VCEP for ATM v1.5.0, only PM2_Supporting is met (allele frequency ≤0.001% in gnomAD v4). All other applicable criteria are either not met or not applicable. With a single supporting-level pathogenic criterion and no benign criteria met, the variant is classified as Uncertain Significance (VUS) per the ACMG/AMP 2015 combining rules as adopted by the ATM VCEP.
No criteria match.
Met · 1
PM2 SupportingThis variant is present at extremely low frequency in gnomAD v4.1 (total AF=2.49e-06; 4/1,605,254 alleles; grpmax FAF=2.8e-07; 0 homozygotes), meeting the ATM VCEP PM2_Supporting threshold of ≤0.001% (≤0.00001) in the gnomAD v4 dataset. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: total AF=2.49e-06 (0.000249%)
- 4 alleles in 1
- 605
- 254
- grpmax FAF=2.8e-07 (0.000028%)
- Highest subpopulation AF: East Asian
- 2.23e-05 (0.00223%)
- 1/44
- 826 alleles
- 0 homozygotes observed
- VCEP threshold: ≤0.001% — met
Sources
Not met · 12 · evaluated, threshold not reached
PS1 PS1 requires a known pathogenic missense variant at the same amino acid residue (p.Thr2754) with a different nucleotide change, and splicing must be ruled out for both. SpliceAI max delta score of 0.01 rules out splicing impact. However, no pathogenic missense comparator at p.Thr2754 has been identified through PM5 candidate review or ClinVar search. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.01 — no predicted splice impact
- PM5 candidate search returned no same-residue pathogenic missense comparators
- ATM VCEP PS1 specification requires splicing ruled out for both alterations
Still missing
- No pathogenic missense comparator at p.Thr2754 identified
Sources
PS3 No variant-specific functional assay data are available for NM_000051.4:c.8261C>T (p.Thr2754Ile). The ATM VCEP requires demonstration that the variant fails to rescue ATM-specific functional features (e.g., phosphorylation of ATM-specific targets) and/or radiosensitivity. OncoKB reports no reviewed functional evidence for this variant, and no publications with functional data for this exact variant were identified. Details ▾Hide ▴
Evidence considered
- OncoKB: no variant-specific reviewed functional evidence
- classification Unknown Oncogenic Effect
- Exploratory search found no direct functional study for c.8261C>T
Still missing
- No functional assay (kinase activity
- radiosensitivity rescue
- or ATM substrate phosphorylation) performed on this variant
Sources
PS4 The ATM VCEP requires a formal case-control study with p-value ≤0.05 and an odds ratio/hazard ratio/relative risk ≥2 or lower 95% CI ≥1.5. No case-control study evaluating this variant's enrichment in ATM-associated cancer or ataxia-telangiectasia cohorts has been identified. The variant is extremely rare in population databases (gnomAD v4.1 AF=2.49e-06), but without case counts, PS4 cannot be applied. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 4/1
- 605
- 254 alleles
- AF=2.49e-06
- No case-control study comparing variant frequency in disease cohorts vs. general population identified
Still missing
- No case-control data or systematic case series comparing this variant in affected vs. unaffected cohorts
Sources
PM3 No evidence of this variant detected in trans with a known pathogenic ATM variant in an individual with ataxia-telangiectasia (A-T) was identified. The ATM VCEP PM3/BP2 framework assigns points based on confirmed trans configuration in A-T probands with confident or consistent phenotype. No such reports were found in ClinVar, literature, or database searches. Details ▾Hide ▴
Evidence considered
- ATM VCEP PM3/BP2 points table requires trans observation in A-T proband
- Exploratory search found no biallelic observations for this variant
- ClinVar submissions do not report compound heterozygosity with a pathogenic ATM variant
Still missing
- No observation of this variant in trans with a pathogenic ATM variant in an A-T patient
Sources
vcep_atm_pm3_bp2_1_5
PP1 No cosegregation data are available for this variant. Under the ATM VCEP, PP1 applies to autosomal recessive conditions (ataxia-telangiectasia) and requires segregation in affected relatives (1=Supporting, 2=Moderate, ≥3=Strong). No family studies or segregation analyses involving this variant have been identified. Details ▾Hide ▴
Evidence considered
- No segregation studies or family cosegregation data identified for this variant
Still missing
- No segregation data in families with A-T or ATM-associated cancer
PP3 The REVEL score for this missense variant is 0.633, which is below the ATM VCEP PP3 threshold of >0.7333. The BayesDel score is -0.0763065. SpliceAI predicts no significant splice impact (max delta score = 0.01, below the 0.2 threshold). None of the ATM VCEP in silico criteria for PP3 are satisfied. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.633 (VCEP threshold: >0.7333 — not met)
- BayesDel score: -0.0763065
- SpliceAI max delta: 0.01 (VCEP threshold: ≥0.2 — not met)
- No predicted splice impact from any in silico tool
Sources
BA1 The ATM VCEP BA1 threshold requires a grpmax filtering allele frequency >0.5% in gnomAD v4. The observed grpmax FAF is 2.8e-07 (0.000028%), which is far below the 0.5% stand-alone benign threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF = 2.8e-07 (0.000028%)
- VCEP BA1 threshold: >0.5% — not met
Sources
BS1 The ATM VCEP BS1 threshold requires a grpmax filtering allele frequency >0.05% in gnomAD v4. The observed grpmax FAF is 2.8e-07 (0.000028%), which is well below the 0.05% strong benign threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF = 2.8e-07 (0.000028%)
- VCEP BS1 threshold: >0.05% — not met
Sources
BS3 No functional evidence demonstrating that this variant rescues ATM-specific function (e.g., phosphorylation of ATM-specific targets) or radiosensitivity has been identified. The ATM VCEP BS3 requires well-established in vitro or in vivo functional studies showing no damaging effect. OncoKB contains no reviewed functional evidence for this variant. Details ▾Hide ▴
Evidence considered
- OncoKB: no variant-specific reviewed functional evidence
- Unknown Oncogenic Effect
- No functional studies showing neutral effect on ATM kinase activity or radiosensitivity
Still missing
- No functional data demonstrating normal ATM activity for this variant
Sources
BP2 No evidence of this variant occurring in trans with a known pathogenic ATM variant in an unaffected (non-A-T) individual has been identified. The ATM VCEP BP2 framework assigns negative points for observations of the variant in trans with pathogenic variants in healthy individuals. No such observations are available in ClinVar, gnomAD homozygote data, or published literature. Details ▾Hide ▴
Evidence considered
- 0 homozygotes in gnomAD v2.1 and v4.1
- No healthy individual reported with this variant in trans with a pathogenic ATM variant
- ATM VCEP BP2 points table requires confirmed trans with pathogenic variant in unaffected individual
Still missing
- No observation in trans with pathogenic ATM variant in unaffected individuals
Sources
BP4 The ATM VCEP BP4 missense threshold requires a REVEL score ≤0.249. This variant has a REVEL score of 0.633, which exceeds the threshold. While SpliceAI predicts no splice impact (max delta=0.01, ≤0.1 meets the splicing BP4 criterion), the missense BP4 criterion takes precedence for a missense variant and is not met. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.633 (VCEP BP4 threshold: ≤0.249 — not met)
- SpliceAI max delta: 0.01 (no predicted splice impact)
- BayesDel score: -0.0763065
Sources
PS5 No de novo observations with confirmed maternity and paternity have been reported for this variant. Under generic ACMG/AMP 2015 rules, PS5 is a supporting-level pathogenic criterion applicable when a de novo observation has been confirmed. No such evidence was found in ClinVar submissions, literature, or database searches. Details ▾Hide ▴
Evidence considered
- No de novo reports identified in ClinVar
- literature
- or database records for this variant
Still missing
- No de novo observation reported
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. This variant (NM_000051.4:c.8261C>T, p.Thr2754Ile) is a missense substitution; the ATM VCEP PVS1 decision tree applies only to null variants (nonsense, frameshift, canonical splice, initiation codon, or exon deletions). Details ▾Hide ▴
Evidence considered
- ATM PVS1 VCEP decision tree requires a null variant class
- this is a missense
- pvs1_variant_assessment confirms variant_bucket='other'
- canonical_splice_consensus=false
Sources
pvs1_gene_contextpvs1_variant_assessmentvcep_atm_pvs1_1_5
PS2 VCEPPS2 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
PM1 VCEPPM1 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
PM4 N/AThe ATM VCEP restricts PM4 to stop-loss variants. NM_000051.4:c.8261C>T is a missense variant (p.Thr2754Ile), not a stop-loss. Details ▾Hide ▴
Evidence considered
- ATM VCEP PM4 specification: 'Use for stop-loss variants'
- This is a missense variant
- not stop-loss
Sources
PM5 N/AThe ATM VCEP PM5 specification applies to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, and to splice variants with PVS1_VS(RNA) where NMD is predicted. This is a missense variant (p.Thr2754Ile) and does not fall into these categories. Classic same-residue missense PM5 is not applied under the ATM VCEP framework. Details ▾Hide ▴
Evidence considered
- ATM VCEP PM5: restricted to truncating/frameshifting variants upstream of p.Arg3047 and qualifying splice variants
- PM5 candidate assessment confirms this is a non-missense framework rule
Sources
cspec ↗pm5_candidates
PM6 VCEPPM6 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
PP2 VCEPPP2 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
PP4 VCEPPP4 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
PP5 VCEPPP5 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
BS2 VCEPBS2 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
BS4 VCEPBS4 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
BP1 VCEPBP1 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
BP3 VCEPBP3 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
BP5 VCEPBP5 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
BP6 VCEPBP6 is listed as Not Applicable by the ClinGen HBOP VCEP for ATM v1.5.0. Details ▾Hide ▴
BP7 N/ABP7 is restricted to synonymous and deep intronic variants per the ATM VCEP specification. NM_000051.4:c.8261C>T is a missense variant (p.Thr2754Ile) and does not qualify for BP7 assessment. Details ▾Hide ▴
Evidence considered
- ATM VCEP BP7: 'Use for synonymous and deep intronic variants'
- This variant is a missense substitution
Sources
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.8261C>T
- Protein (HGVS p.)
- NP_000042.3:p.(Thr2754Ile)
- GRCh38
- chr11:108335954 C>T
- GRCh37
- chr11:108206681 C>T
- ClinVar
- 127457
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
4 / 1,605,254 alleles
AF 2.49e-06 · 0 homozygotes · FAF 2.8e-07
gnomAD v2.1
1 / 31,352 alleles
AF 3.19e-05 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 2.5e-06 · 4 / 1,605,254 alleles · 0 hom · FAF 2.8e-07
| East Asian1 / 44,826 | 2.2e-05 |
| African/African American1 / 74,682 | 1.3e-05 |
| European (non-Finnish)2 / 1,172,242 | 1.7e-06 |
0 alternate alleles recorded in 7 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 3.2e-05 · 1 / 31,352 alleles · 0 hom
| European (non-Finnish)1 / 15,416 | 6.5e-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= 2.49182e-06; MAF= 0.00025%, 4/1605254 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23085e-05; MAF= 0.00223%, 1/44826 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18959e-05; MAF= 0.00319%, 1/31352 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.48677e-05; MAF= 0.00649%, 1/15416 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.633
- BayesDel
- -0.076
How the predictions were used
PP3 The REVEL score for this missense variant is 0.633, which is below the ATM VCEP PP3 threshold of >0.7333. The BayesDel score is -0.0763065. SpliceAI predicts no significant splice impact (max delta score = 0.01, below the 0.2 threshold). None of the ATM VCEP in silico criteria for PP3 are satisfied. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.633 (VCEP threshold: >0.7333 — not met)
- BayesDel score: -0.0763065
- SpliceAI max delta: 0.01 (VCEP threshold: ≥0.2 — not met)
- No predicted splice impact from any in silico tool
Sources
BP4 The ATM VCEP BP4 missense threshold requires a REVEL score ≤0.249. This variant has a REVEL score of 0.633, which exceeds the threshold. While SpliceAI predicts no splice impact (max delta=0.01, ≤0.1 meets the splicing BP4 criterion), the missense BP4 criterion takes precedence for a missense variant and is not met. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.633 (VCEP BP4 threshold: ≤0.249 — not met)
- SpliceAI max delta: 0.01 (no predicted splice impact)
- BayesDel score: -0.0763065
Sources
BP7 N/ABP7 is restricted to synonymous and deep intronic variants per the ATM VCEP specification. NM_000051.4:c.8261C>T is a missense variant (p.Thr2754Ile) and does not qualify for BP7 assessment. Details ▾Hide ▴
Evidence considered
- ATM VCEP BP7: 'Use for synonymous and deep intronic variants'
- This variant is a missense substitution
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.633. BayesDel score = -0.0763065.
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
-
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 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.
-
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 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.
-
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 20301317 ↗PMID:20301317No 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.
-
PMID 20050888 ↗EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.No paper-specific finding is recorded.
-
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
4 / 1,605,254 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
6 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/127457/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108206681-C-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108335954-C-T?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108335954-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.8261…
- OncoKB ↗www.oncokb.org/gene/ATM/T2754I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.8261C%3ET
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.49182e-06; MAF= 0.00025%, 4/1605254 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23085e-05; MAF= 0.00223%, 1/44826 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18959e-05; MAF= 0.00319%, 1/31352 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.48677e-05; MAF= 0.00649%, 1/15416 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (6 clinical laboratories). (ClinVarID = 127457)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.633. BayesDel score = -0.0763065.
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.