About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.5488A>G, p.(Met1830Val)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen ATM VCEP v1.5.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS3Supporting
BS3 · supporting
VCEP-endorsed functional assay data (Table S1, PMID:40580951) classifies M1830V as 'Functional' with 'High' confidence (Combined_score = -0.63; DeepATM_predicted = 'No'), indicating the variant rescues ATM function. Per VCEP BS3 rules, rescue of an ATM-specific feature qualifies for BS3_Supporting.
BP4Supporting
BP4 · supporting
REVEL score = 0.146, which is ≤0.249 meeting the VCEP BP4 threshold for missense variants. SpliceAI max delta = 0.04 ≤ 0.1, indicating no predicted splicing impact. BayesDel = -0.31326. Multiple computational tools consistently predict a benign impact.
Recorded classification: Likely benign
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: BS3 supporting, BP4 supporting; maps to Likely Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
27 / 1,611,638 alleles
gnomAD v4.1: 27 / 1,611,638 alleles. Recorded AF 1.67531e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.1962e-05; MAF= 0.00120%, 3/250794 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000163506; MAF= 0.01635%, 1/6116 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.040 maximum delta
Recorded SpliceAI maximum delta score: 0.040. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
11 reported laboratory submissions
7 Uncertain significance · 4 Likely benign.
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
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: 2 met · 6 not met · 3 not assessed · 18 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.5488A>G (p.Met1830Val) is a missense variant in ATM, a gene in which loss of function is an established mechanism for ataxia telangiectasia (autosomal recessive) and where pathogenic variants confer moderate-risk susceptibility to hereditary breast, ovarian, and pancreatic cancer (autosomal dominant).
This variant is observed in gnomAD v4.1 at an overall allele frequency of 0.001675% (27/1,611,638 alleles; grpmax FAF = 0.0226%), which is rare but above the VCEP PM2 threshold of 0.001%, and does not meet BA1 (>0.5%), BS1 (>0.05%), or PM2_Supporting (≤0.001%) population thresholds.
VCEP-endorsed functional data (Table S1, PMID:40580951) classifies M1830V as 'Functional' with 'High' confidence (Combined_score = -0.63; DeepATM predicted not pathogenic), indicating the variant retains ATM function. This supports BS3_Supporting per VCEP rules.
Computational predictors consistently suggest a benign impact: REVEL = 0.146 (BP4 threshold ≤0.249), BayesDel = -0.31326, AlphaMissense = 0.0733, and SpliceAI max delta = 0.04. This supports BP4_Supporting per VCEP rules.
This variant has been reported in ClinVar as Uncertain significance by 7 clinical laboratories and Likely benign by 4 clinical laboratories (ClinVar Variation ID: 141271). It has been observed as a somatic variant (M1830V, VUS) in a metastatic pancreatic cancer case (PMID:27034805), but this somatic observation does not inform germline classification.
Applying the VCEP HBOP ATM v1.5.0 framework: met criteria include BS3_Supporting and BP4_Supporting (2 benign supporting criteria). No pathogenic criteria are met. Per ACMG/AMP combination rules (Rule 19), ≥2 benign supporting criteria support a classification of Likely Benign.
No criteria match.
Met · 2
BS3 SupportingVCEP-endorsed functional assay data (Table S1, PMID:40580951) classifies M1830V as 'Functional' with 'High' confidence (Combined_score = -0.63; DeepATM_predicted = 'No'), indicating the variant rescues ATM function. Per VCEP BS3 rules, rescue of an ATM-specific feature qualifies for BS3_Supporting. Details ▾Hide ▴
Evidence considered
- VCEP Table S1: Classification='Functional'
- Confidence='High'
- Combined_score=-0.63.
- DeepATM_predicted='No' (not pathogenic).
- VCEP ATM kinase activity and radiosensitivity tables do not include M1830V
- evidence drawn from combined functional score.
Still missing
- VCEP ATM kinase activity and radiosensitivity specific assay tables (clingen_hbop_atm_supplementary_tables_1_and_2_v1.xlsx) do not list M1830V
- BS3 weight is from combined functional score rather than the individual ATM-specific and radiosensitivity rescue assays referenced in VCEP BS3 rules.
Sources
vcep_suppl_tables1_pmid_40580951cspec ↗
BP4 SupportingREVEL score = 0.146, which is ≤0.249 meeting the VCEP BP4 threshold for missense variants. SpliceAI max delta = 0.04 ≤ 0.1, indicating no predicted splicing impact. BayesDel = -0.31326. Multiple computational tools consistently predict a benign impact. Details ▾Hide ▴
Evidence considered
- REVEL = 0.146 (BP4 threshold ≤0.249).
- BayesDel = -0.31326 (benign-leaning).
- SpliceAI max delta = 0.04 (no splicing impact
- threshold ≤0.1).
- AlphaMissense = 0.0733.
- CADD.phred = 18.4.
Sources
Not met · 6 · evaluated, threshold not reached
PS1 No same-amino-acid change at residue 1830 has been established as pathogenic by the ATM VCEP. The VCEP PS1 splicing table applies only to splicing variants, not missense substitutions. SpliceAI delta = 0.04 rules out cryptic splicing concern. Details ▾Hide ▴
Evidence considered
- No pathogenic comparator with same amino acid change (M1830V) identified.
- SpliceAI max delta 0.04 confirms no splicing defect confounds the missense assessment.
Sources
vcep_atm_ps1_1_5spliceai ↗
PS3 VCEP-endorsed functional data (Table S1, PMID:40580951) classifies M1830V as 'Functional' with 'High' confidence and Combined_score = -0.63, indicating retained ATM function. DeepATM predicts 'No' (not pathogenic). No evidence of damaging effect on protein function. Details ▾Hide ▴
Evidence considered
- VCEP Table S1 functional classification: 'Functional' (High confidence)
- Combined_score -0.63
- DeepATM_predicted='No'.
- VCEP ATM kinase activity and radiosensitivity supplementary tables do not list M1830V.
Sources
vcep_suppl_tables1_pmid_40580951cspec ↗
PM2 gnomAD v4.1 allele frequency = 27/1,611,638 (AF = 0.001675%), which exceeds the VCEP PM2_Supporting threshold of ≤0.001%. The variant is present in 27 alleles across population databases, including 4 alleles in the Middle Eastern subpopulation (AF=0.066%). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 27/1
- 611
- 638 alleles (AF=0.001675%)
- grpmax FAF=0.00022553.
- gnomAD v2.1: 3/250
- 794 alleles (AF=0.00120%).
Sources
PP3 REVEL score = 0.146, which is well below the VCEP PP3 threshold of >0.7333 for missense variants. SpliceAI max delta = 0.04, indicating no predicted splicing impact. Multiple in silico tools do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL = 0.146 (threshold >0.7333).
- BayesDel = -0.31326 (benign-leaning).
- SpliceAI max delta = 0.04.
- CADD.phred = 18.4.
- AlphaMissense = 0.0733 (benign-leaning).
Sources
BA1 gnomAD v4.1 grpmax Filtering AF = 0.00022553 (0.0226%), which is far below the VCEP BA1 threshold of >0.5% (grpmax FAF). The variant is not common enough to qualify as a stand-alone benign polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 0.00022553 (0.0226%)
- BA1 threshold >0.5%.
Sources
BS1 gnomAD v4.1 grpmax Filtering AF = 0.00022553 (0.0226%), which is below the VCEP BS1 threshold of >0.05%. The variant is not sufficiently frequent in population databases to support a benign interpretation under BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 0.00022553 (0.0226%)
- BS1 threshold >0.05%.
Sources
Not assessed · 3 · no assessment recorded
PS4 No case-control study data available for this variant. VCEP PS4 requires case-control studies with p≤0.05 and OR≥2 or lower 95% CI ≥1.5. No such evidence was identified. Details ▾Hide ▴
Evidence considered
- No case-control data identified for NM_000051.4:c.5488A>G.
Still missing
- No case-control study evaluating this variant.
Sources
PP1 No segregation data available. VCEP PP1 applies only to AR condition (ataxia telangiectasia) and requires affected relatives with both variants identified. No AT family segregation data were identified for this variant. Details ▾Hide ▴
Evidence considered
- No AT family segregation data identified.
Still missing
- No segregation or family data available.
Sources
BP2 No AT proband data with biallelic co-occurrence in unaffected individuals available. VCEP BP2 requires scoring per the ATM PM3/BP2 table based on unaffected individuals (≥18 years, no A-T) with the variant in trans or homozygous with a P/LP variant. Details ▾Hide ▴
Evidence considered
- No unaffected individual data with biallelic variant co-occurrence identified.
Still missing
- No AT proband or unaffected individual data available for BP2 assessment.
Sources
cspec ↗vcep_atm_pm3_bp2_1_5
Not applicable · 18· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AMissense substitution (p.Met1830Val) is not a null variant. The ATM VCEP PVS1 decision tree applies only to nonsense, frameshift, canonical ±1,2 splice site, initiation codon, or exon deletion variants. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution outside the scope of the PVS1 null-variant framework.
Sources
vcep_atm_pvs1_1_5pvs1_generic_framework ↗
PS2 VCEPATM VCEP specifies PS2 is not applicable: informative de novo occurrences have not 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 occur within the same ATM domains and germline mutational hotspots are not well defined. Details ▾Hide ▴
PM3 N/ARecessive disorder trans-configuration evidence requires AT proband data; no AT proband co-occurrence data reviewed for this variant. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AVCEP PM4 applies only to stop-loss variants; missense substitution does not alter protein length. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AVCEP PM5 applies only to frameshifting/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.' Details ▾Hide ▴
Evidence considered
- VCEP explicitly excludes missense variants from PM5.
- PM5 candidates file confirms truncation-cutoff framework
- not classic missense PM5.
Sources
cspec ↗pm5_candidates
PM6 VCEPATM VCEP specifies PM6 is not applicable: informative de novo occurrences have not 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 benign missense variation. Details ▾Hide ▴
PP4 VCEPATM VCEP specifies PP4 is not applicable: breast cancer has multiple genetic etiologies (genetic heterogeneity) and there are no features that can readily distinguish hereditary from sporadic causes. For AR disease, such evidence is built into the PM3/BP2 table. Details ▾Hide ▴
PP5 VCEPATM VCEP specifies PP5 is not applicable: this criterion 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, so observation in a healthy adult does not provide sufficient evidence for benign classification. Details ▾Hide ▴
BS4 VCEPATM VCEP specifies BS4 is not applicable: lack of segregation analysis in low-penetrance genes can produce false positives (AD), and informative instances of lack of co-segregation in A-T families are too rare for weighting (AR). Details ▾Hide ▴
BP1 VCEPATM VCEP specifies BP1 is not applicable: missense pathogenic variants are known for ATM, so a missense variant cannot be presumed benign solely because truncating variants are the primary disease mechanism. Details ▾Hide ▴
BP3 VCEPIn-frame deletions/insertions in repetitive regions; not applicable to single-nucleotide missense substitutions. Details ▾Hide ▴
No further detail was recorded.
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 with higher tolerance for co-occurring variants in the general population. Details ▾Hide ▴
BP6 VCEPATM VCEP specifies BP6 is not applicable: this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP7 N/AVCEP BP7 applies to synonymous and deep intronic variants (beyond +7 donor and -21 acceptor). This is a missense substitution (c.5488A>G, p.Met1830Val) and does not fall within the BP7 variant scope. Details ▾Hide ▴
Evidence considered
- Missense variant outside the scope of BP7 (synonymous/deep intronic only).
Sources
PS5 N/APS5 is not included in the ATM VCEP criteria set (HBOP VCEP v1.5.0). This criterion is not part of the VCEP framework for ATM variant classification. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.5488A>G
- Protein (HGVS p.)
- NP_000042.3:p.(Met1830Val)
- GRCh38
- chr11:108303021 A>G
- GRCh37
- chr11:108173748 A>G
- ClinVar
- 141271
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
27 / 1,611,638 alleles
AF 1.68e-05 · 0 homozygotes · FAF 0.000226
gnomAD v2.1
3 / 250,794 alleles
AF 1.2e-05 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.7e-05 · 27 / 1,611,638 alleles · 0 hom · FAF 0.00023
| Middle Eastern4 / 6,056 | 0.00066 |
| East Asian7 / 44,790 | 0.00016 |
| African/African American3 / 74,856 | 4e-05 |
| Ashkenazi Jewish1 / 29,572 | 3.4e-05 |
| Admixed American1 / 59,988 | 1.7e-05 |
| Remaining individuals1 / 62,388 | 1.6e-05 |
| European (non-Finnish)10 / 1,178,052 | 8.5e-06 |
0 alternate alleles recorded in 3 other groups: European (Finnish), Amish, South Asian.
gnomAD v2.1
AF 1.2e-05 · 3 / 250,794 alleles · 0 hom
| Remaining individuals1 / 6,116 | 0.00016 |
| East Asian1 / 18,380 | 5.4e-05 |
| European (non-Finnish)1 / 113,264 | 8.8e-06 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.67531e-05; MAF= 0.00168%, 27/1611638 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000660502; MAF= 0.06605%, 4/6056 alleles, homozygotes = 0); grpmax FAF= 0.00022553.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.1962e-05; MAF= 0.00120%, 3/250794 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000163506; MAF= 0.01635%, 1/6116 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.146
- BayesDel
- -0.313
How the predictions were used
BP4 SupportingREVEL score = 0.146, which is ≤0.249 meeting the VCEP BP4 threshold for missense variants. SpliceAI max delta = 0.04 ≤ 0.1, indicating no predicted splicing impact. BayesDel = -0.31326. Multiple computational tools consistently predict a benign impact. Details ▾Hide ▴
Evidence considered
- REVEL = 0.146 (BP4 threshold ≤0.249).
- BayesDel = -0.31326 (benign-leaning).
- SpliceAI max delta = 0.04 (no splicing impact
- threshold ≤0.1).
- AlphaMissense = 0.0733.
- CADD.phred = 18.4.
Sources
PP3 REVEL score = 0.146, which is well below the VCEP PP3 threshold of >0.7333 for missense variants. SpliceAI max delta = 0.04, indicating no predicted splicing impact. Multiple in silico tools do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL = 0.146 (threshold >0.7333).
- BayesDel = -0.31326 (benign-leaning).
- SpliceAI max delta = 0.04.
- CADD.phred = 18.4.
- AlphaMissense = 0.0733 (benign-leaning).
Sources
BP7 N/AVCEP BP7 applies to synonymous and deep intronic variants (beyond +7 donor and -21 acceptor). This is a missense substitution (c.5488A>G, p.Met1830Val) and does not fall within the BP7 variant scope. Details ▾Hide ▴
Evidence considered
- Missense variant outside the scope of BP7 (synonymous/deep intronic only).
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.146. BayesDel score = -0.31326.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
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PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.Analyzes tamoxifen and contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. Does not discuss ATM variants.Does not name this variant
-
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 consensus guidelines for sequence variant interpretation. Provides the general classification framework and combination rules but does not discuss the ATM c.5488A>G variant.Does not name this variant
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Describes a standardized DNA variant scoring system (Sherloc) for pathogenicity assessments in Mendelian disorders. Does not discuss the ATM c.5488A>G variant.Does not name this variant
-
PMID 26667234 ↗Cell-free DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients.Liang DH et al. · 2016Evaluates cell-free DNA as a tool for monitoring disease progression in breast cancer. Reports mutations in TP53, PIK3CA, EGFR, and ERBB2. The ATM c.5488A>G variant was not identified in this paper.Does not name this variant
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PMID 27034805 ↗Molecular profiling of a case of advanced pancreatic cancer identifies an active and tolerable combination of targeted therapy with backbone chemotherapy.Johnson B et al. · 2016Molecular profiling of a metastatic pancreatic cancer case identified ATM M1830V (c.5488A>G) as a variant of unknown significance alongside KRAS G12D, APC T1556fs, and FBXW7 R465H mutations. The variant was detected by NGS on a liver metastasis biopsy and informed a treatment decision combining capecitabine, oxaliplatin, bevacizumab, and vorinostat.Names this variant
Quoted passage
ATM NGS M1830V Variant of unknown significance
Table 1 (Caris molecular profiling of liver biopsy)
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PMID 31672839 ↗Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium.Goggins M et al. · 2020Updated CAPS consortium recommendations for management of individuals at increased risk for familial pancreatic cancer. Mentions ATM as a pancreatic cancer susceptibility gene but does not discuss specific ATM variants.Does not name this variant
-
PMID 32566746 ↗Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome.Reports prevalence of germline pathogenic variants in 28 HBOC susceptibility genes among 568 Japanese BRCA1/2-wildtype patients. ATM showed significant enrichment (OR=2.7-3.6). Identifies several ATM P/LP variants (p.R805*, p.P80fs, p.Q374fs, c.4776+2T>A, p.F1837fs, p.A2626fs) but does not report or evaluate c.5488A>G (M1830V).Does not name this variant
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow D et al. · 2007No 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
27 / 1,611,638 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.040
Open source ↗
ClinVar
7 Uncertain significance · 4 Likely benign
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/141271/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108173748-A-G?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108303021-A-G?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/11-108303021-A-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.5488…
- OncoKB ↗www.oncokb.org/gene/ATM/M1830V
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.5488A%3EG
- 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= 1.67531e-05; MAF= 0.00168%, 27/1611638 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000660502; MAF= 0.06605%, 4/6056 alleles, homozygotes = 0); grpmax FAF= 0.00022553.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.1962e-05; MAF= 0.00120%, 3/250794 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000163506; MAF= 0.01635%, 1/6116 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories) and as Likely benign (4 clinical laboratories). (ClinVarID = 141271)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.146. BayesDel score = -0.31326.
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.