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ATMc.6801C>TNot classified
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Variant interpretation report

ATM c.6801C>T, p.(Asn2267=)

NM_000051.4:c.6801C>T NP_000042.3:p.(Asn2267=) View identifiers
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.

About ATM

No gene-level summary was recorded for this case.

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: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

This variant is absent from gnomAD v2.1 and is present at very low frequency in gnomAD v4.1 (4/1,598,316 alleles; AF 0.00025%), which is below the ATM VCEP PM2 threshold of 0.001%. The highest observed subpopulation count is a single allele in the Remaining individuals population (1/62,100; AF 0.00161%), and the ATM VCEP notes that n=1 in a single subpopulation is sufficiently rare for PM2_Supporting.

Benign criteria applied · 1
BP7Supporting
BP7 · supporting

This variant is a synonymous substitution, p.(Asn2267=) / p.(N2267=), and SpliceAI predicts no significant splice impact (max delta score 0.00), supporting BP7 for a silent ATM variant.

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: PM2 supporting, BP7 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.

SpliceAI score
0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP7 → SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions

2 Likely benign · 1 Benign.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

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
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under ClinGen ATM VCEP v1.5.0, with the data and sources behind each one.

28 criteria with recorded statuses: 2 met · 4 not met · 7 not assessed · 15 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The ATM c.6801C>T (p.Asn2267=; p.N2267=) variant has been reported in ClinVar as likely benign or benign by three clinical laboratory submissions.

This variant is absent from gnomAD v2.1 and gnomAD-Canada and is present at very low frequency in gnomAD v4.1 (4/1,598,316 alleles; AF 0.00025%), which meets the ATM VCEP PM2_Supporting rarity threshold.

SpliceAI predicts no significant splice impact for this synonymous variant (max delta score 0.00), supporting BP7 and not supporting PP3.

Met · 2

PM2 SupportingThis variant is absent from gnomAD v2.1 and is present at very low frequency in gnomAD v4.1 (4/1,598,316 alleles; AF 0.00025%), which is below the ATM VCEP PM2 threshold of 0.001%. The highest observed subpopulation count is a single allele in the Remaining individuals population (1/62,100; AF 0.00161%), and the ATM VCEP notes that n=1 in a single subpopulation is sufficiently rare for PM2_Supporting. Details ▾Hide ▴
Rule
ATM VCEP PM2_Supporting: frequency ≤0.001% in gnomAD v4; n=1 in a single subpopulation also qualifies.
Evidence considered
  • Absent from gnomAD v2.1.
  • gnomAD v4.1 total AF 2.5026340223084796e-06 (0.00025%)
  • 4/1598316 alleles
  • 0 homozygotes.
  • Single allele in highest subpopulation.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BP7 SupportingThis variant is a synonymous substitution, p.(Asn2267=) / p.(N2267=), and SpliceAI predicts no significant splice impact (max delta score 0.00), supporting BP7 for a silent ATM variant. Details ▾Hide ▴
Rule
ATM VCEP BP7 applies to synonymous variants; lack of predicted splice impact supports a benign interpretation.
Evidence considered
  • Synonymous consequence p.(Asn2267=).
  • SpliceAI DS_AG 0.0
  • DS_AL 0.0
  • DS_DG 0.0
  • DS_DL 0.0
  • max delta 0.0.
Sources
cspec ↗spliceai ↗

Not met · 4 · evaluated, threshold not reached

PS1 No evidence was identified that this variant produces the same predicted or observed splice defect as a known pathogenic or likely pathogenic ATM variant, so PS1 is not met. Details ▾Hide ▴
Rule
ATM PS1 splicing table requires a matching splice event to a known P/LP reference variant.
Evidence considered
  • SpliceAI max delta score 0.00.
  • No qualifying PS1 splice comparator was identified.
Sources
cspec ↗vcep_atm_ps1_1_5spliceai ↗
PP3 SpliceAI predicts no significant splice impact for this variant (max delta score 0.00), which is below the ATM VCEP PP3 splicing threshold of 0.2. No additional calibrated predictor score supporting pathogenicity was available for this synonymous change. Details ▾Hide ▴
Rule
ATM VCEP PP3 for splicing requires SpliceAI ≥0.2.
Evidence considered
  • SpliceAI DS_AG 0.0
  • DS_AL 0.0
  • DS_DG 0.0
  • DS_DL 0.0
  • max delta 0.0.
  • REVEL
  • BayesDel
  • and HCI prior were not available.
Sources
cspec ↗spliceai ↗
BA1 The highest observed filtering allele frequency in gnomAD v4.1 is 6.8e-07 (0.000068%), which is far below the ATM VCEP BA1 threshold of greater than 0.5%, so BA1 is not met. Details ▾Hide ▴
Rule
ATM VCEP BA1: grpmax filtering AF >0.5% in gnomAD v4.
Evidence considered
  • gnomAD v4.1 grpmax FAF 6.8e-07.
Sources
cspec ↗gnomad_v4 ↗
BS1 The highest observed filtering allele frequency in gnomAD v4.1 is 6.8e-07 (0.000068%), which is below the ATM VCEP BS1 threshold of greater than 0.05%, so BS1 is not met. Details ▾Hide ▴
Rule
ATM VCEP BS1: grpmax filtering AF >0.05% in gnomAD v4.
Evidence considered
  • gnomAD v4.1 grpmax FAF 6.8e-07.
Sources
cspec ↗gnomad_v4 ↗

Not assessed · 7 · no assessment recorded

PS3 No published functional study was identified showing that this variant fails ATM-specific rescue assays, so PS3 was not assessed. Details ▾Hide ▴
Rule
ATM VCEP PS3 requires failure to rescue ATM-specific functional features, with or without radiosensitivity depending on strength.
Evidence considered
  • No qualifying functional evidence identified.
Still missing
  • No qualifying ATM-specific functional assay for this variant was identified.
Sources
cspec ↗
PS4 No case-control data were identified showing enrichment of this variant in affected individuals, so PS4 was not assessed. Details ▾Hide ▴
Rule
ATM VCEP PS4 requires significant case-control enrichment.
Evidence considered
  • No variant-specific case-control evidence identified.
Still missing
  • No qualifying case-control study for this specific variant was identified.
Sources
cspec ↗
PM3 No evidence was identified that this variant has been observed in trans with a pathogenic ATM variant in an individual with ataxia-telangiectasia, so PM3 was not assessed. Details ▾Hide ▴
Rule
ATM PM3 requires point-based trans observations in A-T probands.
Evidence considered
  • No PM3 point-generating proband data identified.
Still missing
  • No qualifying trans observations in affected individuals were identified.
Sources
cspec ↗vcep_atm_pm3_bp2_1_5
PP1 No segregation data were identified for this variant, so PP1 was not assessed. Details ▾Hide ▴
Rule
ATM VCEP PP1 requires segregation in affected relatives for the recessive condition.
Evidence considered
  • No qualifying segregation evidence identified.
Still missing
  • No family segregation data were identified.
Sources
cspec ↗
BS3 No published functional study was identified showing rescue of ATM-specific function or radiosensitivity for this variant, so BS3 was not assessed. Details ▾Hide ▴
Rule
ATM VCEP BS3 requires rescue in defined ATM functional assays.
Evidence considered
  • No qualifying functional rescue evidence identified.
Still missing
  • No qualifying benign functional assay for this variant was identified.
Sources
cspec ↗
BP2 No evidence was identified that this variant co-occurs in trans with a pathogenic ATM variant in an unaffected individual, so BP2 was not assessed. Details ▾Hide ▴
Rule
ATM BP2 uses a point-based co-occurrence framework in unaffected non-A-T individuals.
Evidence considered
  • No BP2 point-generating co-occurrence data identified.
Still missing
  • No qualifying benign trans or homozygous observation was identified.
Sources
cspec ↗vcep_atm_pm3_bp2_1_5
BP4 SpliceAI predicts no significant splice impact for this variant (max delta score 0.00), which is below the ATM VCEP BP4 threshold of 0.1, but this silent variant is more specifically addressed by BP7 and BP4 was not counted separately to avoid double counting the same computational evidence. Details ▾Hide ▴
Rule
ATM VCEP BP4 for splicing uses SpliceAI ≤0.1, but overlapping silent-variant evidence is preferentially captured under BP7.
Evidence considered
  • SpliceAI max delta score 0.00.
  • Variant is synonymous.
Sources
cspec ↗spliceai ↗
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is a synonymous substitution, p.(Asn2267=) / p.(N2267=), and does not fall into the ATM PVS1 null-variant categories or the generic canonical ±1,2 splice consensus categories, so PVS1 is not applicable. Details ▾Hide ▴
Rule
ATM PVS1 decision tree; not applicable to non-null synonymous variants outside canonical splice consensus.
Evidence considered
  • Synonymous consequence p.(Asn2267=).
  • Generic PVS1 scaffold states this variant is not in a default null-variant bucket.
Sources
cspec ↗vcep_atm_pvs1_1_5pvs1_gene_contextpvs1_variant_assessment
PS2 VCEPThe ATM VCEP marks PS2 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: PS2 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
PM1 VCEPThe ATM VCEP marks PM1 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: PM1 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
PM4 N/AThis variant is not a stop-loss variant, so PM4 is not applicable. Details ▾Hide ▴
Rule
ATM VCEP PM4 is for stop-loss variants.
Evidence considered
  • Synonymous substitution p.(Asn2267=).
Sources
cspec ↗
PM5 N/AUnder the ATM VCEP, PM5 is used for truncating or qualifying splice variants upstream of p.Arg3047 rather than classic same-residue missense logic, and this synonymous variant does not meet that rule. Details ▾Hide ▴
Rule
ATM VCEP PM5 applies to qualifying truncating or splice variants upstream of p.Arg3047.
Evidence considered
  • PM5 mode is truncation-cutoff gene-specific.
  • Variant is synonymous
  • not truncating or qualifying splice.
Sources
cspec ↗pm5_candidates
PM6 VCEPThe ATM VCEP marks PM6 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: PM6 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
PP2 VCEPThe ATM VCEP marks PP2 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: PP2 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
PP4 VCEPThe ATM VCEP marks PP4 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: PP4 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
PP5 VCEPThe ATM VCEP marks PP5 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: PP5 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
BS2 VCEPThe ATM VCEP marks BS2 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: BS2 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
BS4 VCEPThe ATM VCEP marks BS4 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: BS4 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
BP1 VCEPThe ATM VCEP marks BP1 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: BP1 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
BP3 VCEPThe ATM VCEP marks BP3 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: BP3 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
BP5 VCEPThe ATM VCEP marks BP5 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: BP5 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗
BP6 VCEPThe ATM VCEP marks BP6 as not applicable for this framework. Details ▾Hide ▴
VCEP rule
ATM VCEP: BP6 not applicable.
Evidence considered
  • ATM VCEP applicability table.
Sources
cspec ↗

Identifiers

Gene
ATM
Transcript
NM_000051.4
Coding (HGVS c.)
NM_000051.4:c.6801C>T
Protein (HGVS p.)
NP_000042.3:p.(Asn2267=)
GRCh38
chr11:108325538 C>T
GRCh37
chr11:108196265 C>T
ClinVar
1113077

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…
gnomAD v4.1 4 / 1,598,316 alleles AF 2.5e-06 · 0 homozygotes · FAF 6.8e-07
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 2.5e-06 · 4 / 1,598,316 alleles · 0 hom · FAF 6.8e-07
Remaining individuals1 / 62,100 1.6e-05
European (non-Finnish)3 / 1,168,036 2.6e-06
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 2.50263e-06; MAF= 0.00025%, 4/1598316 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 1.61031e-05; MAF= 0.00161%, 1/62100 alleles, homozygotes = 0); grpmax FAF= 6.8e-07.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -147 bp
0.000
SpliceAI acceptor gainat -228 bp
0.000
SpliceAI donor lossat +6 bp
0.000
SpliceAI donor gainat +3 bp
0.000
Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP7 SupportingThis variant is a synonymous substitution, p.(Asn2267=) / p.(N2267=), and SpliceAI predicts no significant splice impact (max delta score 0.00), supporting BP7 for a silent ATM variant. Details ▾Hide ▴
Rule
ATM VCEP BP7 applies to synonymous variants; lack of predicted splice impact supports a benign interpretation.
Evidence considered
  • Synonymous consequence p.(Asn2267=).
  • SpliceAI DS_AG 0.0
  • DS_AL 0.0
  • DS_DG 0.0
  • DS_DL 0.0
  • max delta 0.0.
Sources
cspec ↗spliceai ↗
PP3 SpliceAI predicts no significant splice impact for this variant (max delta score 0.00), which is below the ATM VCEP PP3 splicing threshold of 0.2. No additional calibrated predictor score supporting pathogenicity was available for this synonymous change. Details ▾Hide ▴
Rule
ATM VCEP PP3 for splicing requires SpliceAI ≥0.2.
Evidence considered
  • SpliceAI DS_AG 0.0
  • DS_AL 0.0
  • DS_DG 0.0
  • DS_DL 0.0
  • max delta 0.0.
  • REVEL
  • BayesDel
  • and HCI prior were not available.
Sources
cspec ↗spliceai ↗
BP4 SpliceAI predicts no significant splice impact for this variant (max delta score 0.00), which is below the ATM VCEP BP4 threshold of 0.1, but this silent variant is more specifically addressed by BP7 and BP4 was not counted separately to avoid double counting the same computational evidence. Details ▾Hide ▴
Rule
ATM VCEP BP4 for splicing uses SpliceAI ≤0.1, but overlapping silent-variant evidence is preferentially captured under BP7.
Evidence considered
  • SpliceAI max delta score 0.00.
  • Variant is synonymous.
Sources
cspec ↗spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

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

  • 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 34242744 ↗
  • Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.
    Trepanier A et al. · 2004
    No paper-specific finding is recorded.
    PMID 15604628 ↗
  • Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors.
    Berliner JL et al. · 2007
    No paper-specific finding is recorded.
    PMID 17508274 ↗
  • The emerging landscape of breast cancer susceptibility.
    Stratton MR et al. · 2008
    No paper-specific finding is recorded.
    PMID 18163131 ↗
  • Hereditary Ataxia Overview.
    Adam MP et al. · 1993
    No paper-specific finding is recorded.
    PMID 20301317 ↗
  • BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.
    Adam MP et al. · 1993
    No paper-specific finding is recorded.
    PMID 20301425 ↗
  • Ataxia-Telangiectasia.
    Adam MP et al. · 1993
    No paper-specific finding is recorded.
    PMID 20301790 ↗
  • Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.
    Moyer VA et al. · 2014
    No paper-specific finding is recorded.
    PMID 24366376 ↗
  • EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.
    Gasser T et al. · 2010
    No paper-specific finding is recorded.
    PMID 20050888 ↗
  • Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
    No paper-specific finding is recorded.
    PMID 28492532 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 4 / 1,598,316 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗
ClinVar 2 Likely benign · 1 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

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= 2.50263e-06; MAF= 0.00025%, 4/1598316 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 1.61031e-05; MAF= 0.00161%, 1/62100 alleles, homozygotes = 0); grpmax FAF= 6.8e-07.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 1113077)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

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.