About ATM
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ATM c.5600A>G, p.(Gln1867Arg)
Classification
Not classified
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. Select a step to read what it means.
Not classified yet.Select a step to read what it means.
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: 2
Benign evidence criteria: 1
Pathogenic criteria applied · 2
PS3Supporting
PS3 · supporting
The ATM VCEP supplementary functional data (Suppl_TableS1, PMID 40580951) classifies NM_000051.4:c.5600A>G (p.Q1867R) as 'Non-functional' with Medium-high confidence based on a combined function score of -2.05 integrating multiple functional predictors. This meets the VCEP PS3_Supporting threshold for a variant that fails to rescue an ATM-specific functional feature. No direct experimental rescue assay data (kinase activity or radiosensitivity) from the VCEP-approved functional studies (Mitui 2009, Barone 2009, Scott 2002) was identified for this exact variant.
PM2Supporting
PM2 · supporting
NM_000051.4:c.5600A>G is present at an extremely low frequency in gnomAD v4.1 (AF = 1.8588e-06, 0.000186%, 3/1,613,944 alleles, 0 homozygotes). This is below the VCEP PM2_Supporting threshold of ≤0.001% (≤1e-5). The variant is absent from gnomAD v2.1 and gnomAD-Canada.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
The ATM VCEP BP4 threshold for missense variants is REVEL ≤ 0.249. NM_000051.4:c.5600A>G (p.Q1867R) has a REVEL score of 0.088, meeting the BP4_Supporting threshold. Additionally, the SpliceAI max delta score is 0.10, which is ≤0.1, meeting the VCEP BP4 splicing threshold (no predicted splicing impact). BayesDel score of -0.34033 also supports a benign computational prediction.
Recorded classification: Not classified
Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule31 (Benign.Supporting >=1 + Pathogenic.Supporting >=1) with applied criteria: PS3 supporting, PM2 supporting, BP4 supporting; maps to Uncertain Significance - Conflicting Evidence.
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
3 / 1,613,944 alleles
gnomAD v4.1: 3 / 1,613,944 alleles. Recorded AF 1.8588e-06. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI score
0.100 maximum delta
Recorded SpliceAI maximum delta score: 0.100. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
4 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
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.
26 criteria with recorded statuses: 3 met · 8 not met · 0 not assessed · 15 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.5600A>G (p.Gln1867Arg) is a missense variant in exon 37 of ATM. It has been reported in ClinVar as a variant of uncertain significance (ClinVar ID 453589, 4 clinical laboratories).
This variant is present in gnomAD v4.1 at an extremely low allele frequency (AF = 1.86e-6, 3/1,613,944 alleles, 0 homozygotes) and is absent from gnomAD v2.1 and gnomAD-Canada, meeting the ATM VCEP PM2_Supporting threshold (≤0.001%).
The ATM VCEP supplementary functional data (Suppl_TableS1, PMID 40580951) classifies this variant as 'Non-functional' (combined score -2.05, Medium-high confidence), meeting PS3_Supporting per the VCEP framework for variants that fail to rescue ATM-specific functional features.
Multiple computational predictors suggest a benign effect: REVEL score 0.088 (meeting BP4_Supporting threshold ≤0.249), BayesDel -0.34033, AlphaMissense 0.0758. SpliceAI predicts no splicing impact (max delta 0.10, meeting BP4 splicing threshold ≤0.1).
No case-control studies, co-segregation data, or confirmed de novo observations have been identified for this variant. A ClinVar submission noting observation in trans with a pathogenic ATM variant in an A-T patient was not accompanied by peer-reviewed publication, precluding application of PM3.
The variant has not been reported in COSMIC and is not located in a statistically significant cancer hotspot residue.
No criteria match.
Met · 3
PS3 SupportingThe ATM VCEP supplementary functional data (Suppl_TableS1, PMID 40580951) classifies NM_000051.4:c.5600A>G (p.Q1867R) as 'Non-functional' with Medium-high confidence based on a combined function score of -2.05 integrating multiple functional predictors. This meets the VCEP PS3_Supporting threshold for a variant that fails to rescue an ATM-specific functional feature. No direct experimental rescue assay data (kinase activity or radiosensitivity) from the VCEP-approved functional studies (Mitui 2009, Barone 2009, Scott 2002) was identified for this exact variant. Details ▾Hide ▴
Evidence considered
- Suppl_TableS1 (PMID 40580951): Combined_score -2.05
- Classification 'Non-functional'
- Confidence 'Medium-high'
- REVEL 0.088
- AlphaMissense 0.0758
- boostDM 0.30
- EVE 0.41.
Still missing
- No direct kinase activity or radiosensitivity rescue assay result for this exact variant in the three VCEP-approved functional studies.
Sources
vcep_suppl_tables1_pmid_40580951vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1
PM2 SupportingNM_000051.4:c.5600A>G is present at an extremely low frequency in gnomAD v4.1 (AF = 1.8588e-06, 0.000186%, 3/1,613,944 alleles, 0 homozygotes). This is below the VCEP PM2_Supporting threshold of ≤0.001% (≤1e-5). The variant is absent from gnomAD v2.1 and gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 3/1
- 613
- 944 alleles (AF 1.8588e-06)
- absent from gnomAD v2.1 and gnomAD-Canada
- highest subpopulation AF in Remaining individuals (1.6005e-05 / 1/62
- 480).
Sources
BP4 SupportingThe ATM VCEP BP4 threshold for missense variants is REVEL ≤ 0.249. NM_000051.4:c.5600A>G (p.Q1867R) has a REVEL score of 0.088, meeting the BP4_Supporting threshold. Additionally, the SpliceAI max delta score is 0.10, which is ≤0.1, meeting the VCEP BP4 splicing threshold (no predicted splicing impact). BayesDel score of -0.34033 also supports a benign computational prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.088 ≤ 0.249 (BP4 threshold for missense)
- SpliceAI max delta 0.10 ≤ 0.1 (no predicted splicing impact)
- BayesDel -0.34033.
Sources
Not met · 8 · evaluated, threshold not reached
PS1 PS1 requires the same amino acid change (p.Gln1867Arg) to be produced by a different nucleotide change already classified as pathogenic or likely pathogenic. Review of ClinVar and VCEP supplementary tables identified no alternative nucleotide variant encoding p.Q1867R with a P/LP classification. Adjacent missense changes at codon 1867 (p.Q1867K, p.Q1867E, p.Q1867P, p.Q1867L, p.Q1867H) are not the same amino acid change. Details ▾Hide ▴
Evidence considered
- No alternative nucleotide change producing p.Q1867R identified
- other codon 1867 missense variants are different amino acid substitutions.
Sources
vcep_suppl_tables1_pmid_40580951clinvar ↗
PS4 The ATM VCEP requires case-control studies demonstrating a statistically significant enrichment (p ≤ 0.05 AND OR ≥ 2 or lower 95% CI ≥ 1.5). No case-control study or proband-counting analysis for NM_000051.4:c.5600A>G has been identified in the literature or ClinVar submissions. The variant has been reported in ClinVar as Uncertain significance and is extremely rare in gnomAD, but population frequency data alone cannot substitute for a formal case-control comparison. Details ▾Hide ▴
Evidence considered
- ClinVar: 4 clinical labs
- all VUS
- no case-control study identified in literature or ClinVar submissions.
Still missing
- No case-control study comparing variant prevalence in ATM-related disease versus controls.
Sources
PP1 The ATM VCEP applies PP1 only for autosomal recessive conditions (Ataxia-Telangiectasia) and requires segregation of both variants in affected relatives. No published segregation data or family studies involving NM_000051.4:c.5600A>G have been identified in the literature or ClinVar submissions. Details ▾Hide ▴
Evidence considered
- No co-segregation data in affected family members identified in any source.
Still missing
- No segregation analysis or family studies for this variant.
Sources
PP3 The ATM VCEP PP3 threshold for missense variants is REVEL > 0.7333. The REVEL score for NM_000051.4:c.5600A>G (p.Q1867R) is 0.088, well below this threshold. The SpliceAI max delta score is 0.10, below the VCEP splicing threshold of ≥0.2. Multiple computational predictors (BayesDel -0.34033, AlphaMissense 0.0758) are consistent with a benign or non-damaging prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.088 (threshold >0.7333)
- SpliceAI max delta 0.10 (threshold ≥0.2)
- BayesDel -0.34033
- AlphaMissense 0.0758.
Sources
BA1 The ATM VCEP BA1 threshold requires a Grpmax Filtering AF > 0.5% in the gnomAD v4 dataset. NM_000051.4:c.5600A>G has an overall allele frequency of 0.000186% (1.8588e-06) in gnomAD v4.1, far below the BA1 stand-alone benign threshold. The grpmax filtering allele frequency is not available (null), but the total AF is orders of magnitude below the BA1 cutoff. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 total AF 1.8588e-06 (0.000186%)
- grpmax_faf null
- far below BA1 threshold of >0.5%.
Sources
BS1 The ATM VCEP BS1 threshold requires a Grpmax Filtering AF > 0.05% in gnomAD v4. The overall allele frequency is 0.000186%, and the grpmax filtering AF is unavailable (null). The total frequency is far below the BS1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 total AF 0.000186%
- grpmax_faf null
- far below BS1 threshold of >0.05%.
Still missing
- gnomAD v4.1 grpmax filtering AF not available for this variant.
Sources
BS3 The ATM VCEP BS3 requires a well-established functional assay demonstrating no damaging effect (variant rescues ATM function). The Suppl_TableS1 (PMID 40580951) classifies NM_000051.4:c.5600A>G as 'Non-functional' with Medium-high confidence, indicating the variant fails to rescue function — the opposite of what BS3 requires. Additionally, multiple in silico predictors (REVEL 0.088, BayesDel -0.34033, AlphaMissense 0.0758) suggest a benign/non-damaging effect, but in silico predictions alone do not meet the VCEP BS3 threshold for well-established functional evidence. Details ▾Hide ▴
Evidence considered
- Suppl_TableS1 classifies variant as 'Non-functional' (fails to rescue) — this supports PS3
- not BS3
- REVEL 0.088
- BayesDel -0.34033 suggest benign effect but are not functional assay data.
Still missing
- No well-established functional assay demonstrating retained normal ATM function for this variant.
Sources
vcep_suppl_tables1_pmid_40580951revelbayesdel
BP2 The ATM VCEP BP2 requires observation of the variant in cis with a pathogenic/likely pathogenic variant in an unaffected individual aged ≥18 years with no evidence of A-T, scored via the PM3/BP2 points table. No such phasing data or unaffected individual observations have been identified for NM_000051.4:c.5600A>G. A ClinVar submission noting co-occurrence in trans with a pathogenic variant in an A-T patient is the opposite configuration (supports PM3, not BP2). Details ▾Hide ▴
Evidence considered
- No observation in cis with P/LP variant in unaffected individual
- ClinVar observation of trans with pathogenic variant in A-T patient is relevant to PM3
- not BP2.
Still missing
- No phasing data confirming cis configuration with a pathogenic ATM variant in a healthy adult.
Sources
clinvar ↗vcep_atm_pm3_bp2_1_5
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is applicable only to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, exon deletions). NM_000051.4:c.5600A>G is a missense variant (p.Gln1867Arg) and does not meet the VCEP ATM PVS1 decision tree entry criteria. SpliceAI max delta score is 0.10, confirming no cryptic splice-altering effect. Details ▾Hide ▴
Evidence considered
- Missense variant p.Gln1867Arg
- SpliceAI delta 0.10 — no predicted splice impact
- does not meet PVS1 null-variant entry criteria per ATM VCEP v1.5.0 PVS1 decision tree.
Sources
spliceai ↗vcep_atm_pvs1_1_5
PS2 VCEPThe ATM VCEP v1.5.0 does not use PS2 for autosomal dominant or autosomal recessive disease; 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 VCEPThe ATM VCEP does not use PM1; benign and pathogenic variants are known to occur within the same domains and germline mutational hotspots are not well defined for ATM at this time. Details ▾Hide ▴
PM5 N/AThe ATM VCEP restricts PM5 to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, and splice variants with PTC upstream of p.Arg3047 where PVS1(RNA) is applied. Missense changes are explicitly excluded: 'Do not use for missense changes.' NM_000051.4:c.5600A>G is a missense variant (p.Gln1867Arg). Details ▾Hide ▴
Evidence considered
- Missense variant
- VCEP explicitly prohibits PM5 for missense changes
- PM5 candidates file confirms truncation-cutoff mode only.
Sources
cspec ↗pm5_candidates
PM6 VCEPThe ATM VCEP v1.5.0 does not use PM6 for autosomal dominant or autosomal recessive disease; informative de novo occurrences have not been observed for ATM and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PP2 VCEPThe ATM VCEP does not use PP2; ATM does not have a defined low rate of missense benign variation. Details ▾Hide ▴
PP4 VCEPThe ATM VCEP does not use PP4. For autosomal dominant disease: breast cancer has multiple genetic etiologies and no features distinguish hereditary from sporadic cases. For autosomal recessive: such evidence is built into the PM3/BP2 table. Details ▾Hide ▴
PP5 VCEPPP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee; this criterion is not applicable for this VCEP. Details ▾Hide ▴
BS2 VCEPThe ATM VCEP does not use BS2 because ATM has incomplete penetrance. Details ▾Hide ▴
Evidence considered
- VCEP explicitly marks BS2 as not applicable due to incomplete penetrance.
Sources
BS4 VCEPThe ATM VCEP does not use BS4. For AD: co-segregation analysis in low-penetrance genes can lead to false positives. For AR: informative instances of lack of co-segregation in A-T families are too rare to be considered. Details ▾Hide ▴
BP1 VCEPThe ATM VCEP does not use BP1; missense pathogenic variants are known for ATM. Details ▾Hide ▴
BP5 VCEPThe ATM VCEP does not use BP5; cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and ATM has low penetrance with higher tolerance in the general population. Details ▾Hide ▴
BP6 VCEPBP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee; this criterion is not applicable for this VCEP. Details ▾Hide ▴
BP7 N/AThe ATM VCEP restricts BP7 to synonymous and deep intronic variants (further than +7 at donor and -21 at acceptor sites). NM_000051.4:c.5600A>G is a missense variant (p.Gln1867Arg) located in exon 37 and does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant in exon 37
- BP7 is restricted to synonymous/deep intronic variants per VCEP.
Sources
PS5 N/APP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee; this criterion is not applicable for this VCEP. Details ▾Hide ▴
Identifiers
- Gene
- ATM
- Transcript
- NM_000051.4
- Coding (HGVS c.)
- NM_000051.4:c.5600A>G
- Protein (HGVS p.)
- NP_000042.3:p.(Gln1867Arg)
- GRCh38
- chr11:108304778 A>G
- GRCh37
- chr11:108175505 A>G
- ClinVar
- 453589
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
3 / 1,613,944 alleles
AF 1.86e-06 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 1.9e-06 · 3 / 1,613,944 alleles · 0 hom
| Remaining individuals1 / 62,480 | 1.6e-05 |
| South Asian1 / 91,090 | 1.1e-05 |
| European (non-Finnish)1 / 1,180,002 | 8.5e-07 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.8588e-06; MAF= 0.00019%, 3/1613944 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 1.60051e-05; MAF= 0.00160%, 1/62480 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.088
- BayesDel
- -0.340
How the predictions were used
BP4 SupportingThe ATM VCEP BP4 threshold for missense variants is REVEL ≤ 0.249. NM_000051.4:c.5600A>G (p.Q1867R) has a REVEL score of 0.088, meeting the BP4_Supporting threshold. Additionally, the SpliceAI max delta score is 0.10, which is ≤0.1, meeting the VCEP BP4 splicing threshold (no predicted splicing impact). BayesDel score of -0.34033 also supports a benign computational prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.088 ≤ 0.249 (BP4 threshold for missense)
- SpliceAI max delta 0.10 ≤ 0.1 (no predicted splicing impact)
- BayesDel -0.34033.
Sources
PP3 The ATM VCEP PP3 threshold for missense variants is REVEL > 0.7333. The REVEL score for NM_000051.4:c.5600A>G (p.Q1867R) is 0.088, well below this threshold. The SpliceAI max delta score is 0.10, below the VCEP splicing threshold of ≥0.2. Multiple computational predictors (BayesDel -0.34033, AlphaMissense 0.0758) are consistent with a benign or non-damaging prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.088 (threshold >0.7333)
- SpliceAI max delta 0.10 (threshold ≥0.2)
- BayesDel -0.34033
- AlphaMissense 0.0758.
Sources
BP7 N/AThe ATM VCEP restricts BP7 to synonymous and deep intronic variants (further than +7 at donor and -21 at acceptor sites). NM_000051.4:c.5600A>G is a missense variant (p.Gln1867Arg) located in exon 37 and does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant in exon 37
- BP7 is restricted to synonymous/deep intronic variants per VCEP.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.10). REVEL score = 0.088. BayesDel score = -0.34033.
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 20301317 ↗Hereditary Ataxia Overview.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20301790 ↗Ataxia-Telangiectasia.Adam MP et al. · 1993No paper-specific finding is recorded.
-
PMID 24418350 ↗EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood.van de Warrenburg BP et al. · 2014No paper-specific finding is recorded.
-
PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015No paper-specific finding is recorded.
-
PMID 26389210 ↗Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002No paper-specific finding is recorded.
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002No paper-specific finding is recorded.
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PMID 29939840 ↗Recommendations on Disease Management for Patients With Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: ASCO Clinical Practice Guideline Update.Ramakrishna N et al. · 2018No paper-specific finding is recorded.
-
PMID 20050888 ↗EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.Gasser T et al. · 2010No 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
3 / 1,613,944 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.100
Open source ↗
ClinVar
4 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/453589/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/11-108175505-A-G?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr11-108304778-A-G?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000051.4%3Ac.5600…
- OncoKB ↗www.oncokb.org/gene/ATM/Q1867R
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ATM+c.5600A%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= 1.8588e-06; MAF= 0.00019%, 3/1613944 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 1.60051e-05; MAF= 0.00160%, 1/62480 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories). (ClinVarID = 453589)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.10). REVEL score = 0.088. BayesDel score = -0.34033.
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.