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ATMc.7927+13T>ALikely benign
Print report
Variant interpretation report

ATM c.7927+13T>A, p.?

NM_000051.4:c.7927+13T>A NP_000042.3:p.? View identifiers
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.

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: 2
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

c.7927+13T>A is present at extremely low frequency in gnomAD v4.1 (AF = 0.00075%, 12/1,609,596 alleles, 0 homozygotes; grpmax FAF = 5.01e-06). This frequency is ≤0.001%, meeting the ATM HBOP VCEP threshold for PM2_Supporting.

Benign criteria applied · 2
BP4Supporting
BP4 · supporting

SpliceAI predicts no splicing impact for c.7927+13T>A (max delta score = 0.03). This is ≤0.1, meeting the ATM HBOP VCEP BP4 threshold for no predicted splicing impact.

BP7Supporting
BP7 · supporting

c.7927+13T>A is an intronic variant at the donor +13 position, which is further than (but not including) +7. This meets the ATM HBOP VCEP BP7 definition for deep intronic variants unlikely to affect splicing.

Recorded classification: Likely benign

Richards et.al., 2015 - Combining rules v1.5.0 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: PM2 supporting, BP4 supporting, BP7 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
12 / 1,609,596 alleles

gnomAD v4.1: 12 / 1,609,596 alleles. Recorded AF 7.45529e-06. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 8.05069e-06; MAF= 0.00081%, 2/248426 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.768e-05; MAF= 0.00177%, 2/113122 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.030 maximum delta

Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

Context only ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗
Somatic evidence
1 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV53773587, n = 1 times).

Context only COSMIC ↗
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 · 10 not met · 0 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP4BP5BP6BP7
Met Not met Not assessed Not applicable

c.7927+13T>A is present at extremely low frequency in gnomAD v4.1 (AF = 0.00075%, 12/1,609,596 alleles, 0 homozygotes; grpmax FAF = 5.01e-06), meeting the ATM HBOP VCEP threshold for PM2_Supporting (≤0.001%).

SpliceAI predicts no significant splicing impact (max delta score = 0.03), meeting BP4_Supporting per the ATM HBOP VCEP threshold of ≤0.1.

The variant is at the donor +13 position, beyond the +7 deep intronic boundary, meeting BP7_Supporting per the ATM HBOP VCEP as a deep intronic variant unlikely to affect splicing.

Two lines of benign supporting evidence (BP4, BP7) are present. Applying ACMG/AMP 2015 combination rules (Richards et al. 2015, PMID:25741868), two benign supporting criteria meet the threshold for Likely Benign (Rule 19).

Met · 3

PM2 Supportingc.7927+13T>A is present at extremely low frequency in gnomAD v4.1 (AF = 0.00075%, 12/1,609,596 alleles, 0 homozygotes; grpmax FAF = 5.01e-06). This frequency is ≤0.001%, meeting the ATM HBOP VCEP threshold for PM2_Supporting. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 AF = 7.46e-06 (0.00075%)
  • 12/1
  • 609
  • 596 alleles
  • grpmax FAF = 5.01e-06 (0.000501%)
Sources
gnomad_v4 ↗cspec ↗
BP4 SupportingSpliceAI predicts no splicing impact for c.7927+13T>A (max delta score = 0.03). This is ≤0.1, meeting the ATM HBOP VCEP BP4 threshold for no predicted splicing impact. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.03 (≤0.1 threshold)
Sources
spliceai ↗cspec ↗
BP7 Supportingc.7927+13T>A is an intronic variant at the donor +13 position, which is further than (but not including) +7. This meets the ATM HBOP VCEP BP7 definition for deep intronic variants unlikely to affect splicing. Details ▾Hide ▴
Evidence considered
  • Variant located at donor +13
  • beyond the +7 deep intronic threshold
Sources
cspec ↗

Not met · 10 · evaluated, threshold not reached

PVS1 NM_000051.4:c.7927+13T>A is an intronic substitution at the donor +13 position, outside the canonical ±1,2 splice consensus. SpliceAI predicts no significant splice impact (max delta score = 0.03). The ATM HBOP VCEP PVS1 decision tree requires either a predicted or observed splice defect; neither is present for this variant. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.03
  • Variant is at donor +13
  • not ±1
  • 2
Sources
spliceai ↗vcep_atm_pvs1_1_5
PS1 No comparator pathogenic or likely pathogenic splicing variant with a similar predicted splicing event has been identified for c.7927+13T>A. The ATM PS1 splicing table requires a reference P/LP variant with matching predicted event, which is not available. Details ▾Hide ▴
Evidence considered
  • No P/LP comparator variant identified at this donor motif
Still missing
  • No comparator splicing variant available for PS1 assessment
Sources
vcep_atm_ps1_1_5
PS3 No well-established in vitro or in vivo functional studies demonstrating a damaging effect on ATM protein function or splicing have been identified for c.7927+13T>A. Details ▾Hide ▴
Evidence considered
  • No functional data available for this variant
Still missing
  • No functional studies identified for this specific variant
PS4 No case-control studies demonstrating significant enrichment of c.7927+13T>A in affected individuals versus controls have been identified. The ATM VCEP requires a case-control study with p-value ≤0.05 and OR/HR/RR ≥2 or lower 95% CI ≥1.5. Details ▾Hide ▴
Evidence considered
  • No case-control data available
Still missing
  • No case-control studies identified for this variant
PP1 No segregation data are available for c.7927+13T>A. The ATM VCEP applies PP1 only for autosomal recessive conditions with segregation in affected relatives; AD co-segregation is not used due to low penetrance. Details ▾Hide ▴
Evidence considered
  • No segregation data available
Still missing
  • No family segregation data identified
PP3 SpliceAI predicts no significant splicing impact (max delta score = 0.03). The ATM HBOP VCEP PP3 threshold for splicing variants is SpliceAI ≥0.2, which is not met. No other computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.03 (<0.2 threshold)
Sources
spliceai ↗cspec ↗
BA1 gnomAD v4.1 grpmax filtering allele frequency is 5.01e-06 (0.000501%), which is not >0.5%. The ATM HBOP VCEP BA1 threshold is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 grpmax FAF = 0.000501% (<0.5% threshold)
Sources
gnomad_v4 ↗cspec ↗
BS1 gnomAD v4.1 grpmax filtering allele frequency is 5.01e-06 (0.000501%), which is not >0.05%. The ATM HBOP VCEP BS1 threshold is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 grpmax FAF = 0.000501% (<0.05% threshold)
Sources
gnomad_v4 ↗cspec ↗
BS3 No well-established in vitro or in vivo functional studies demonstrating no damaging effect on ATM protein function or splicing have been identified for c.7927+13T>A. Details ▾Hide ▴
Evidence considered
  • No functional data available for this variant
Still missing
  • No functional studies identified
BP2 No data are available regarding observation of c.7927+13T>A in trans with a pathogenic ATM variant in unaffected individuals. The ATM PM3/BP2 table requires proband-level data to assign points; none are available. Details ▾Hide ▴
Evidence considered
  • No in trans or homozygous unaffected individual data available
Still missing
  • No proband-level phase data available for BP2 assessment
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPATM HBOP VCEP does not permit use of PS2 for autosomal dominant or autosomal recessive disease; informative de novo occurrences have not been observed for ATM. Details ▾Hide ▴
Sources
cspec ↗
PM1 VCEPATM HBOP VCEP does not permit use of PM1; benign and pathogenic variants are known to occur within the same domains and germline mutational hotspots are not well defined. Details ▾Hide ▴
Sources
cspec ↗
PM5 N/AATM HBOP VCEP PM5 applies only to frameshifting or truncating variants with premature termination codons upstream of p.Arg3047, or to splice variants with PVS1_VS(RNA) applied based on high-quality observed splicing impact. c.7927+13T>A is an intronic substitution at +13 and does not meet either condition. Details ▾Hide ▴
Evidence considered
  • Intronic substitution
  • not frameshift/truncation
  • No PVS1_VS(RNA) applied
Sources
cspec ↗
PM6 VCEPATM HBOP VCEP does not permit use of PM6; informative de novo occurrences have not been observed for ATM. Details ▾Hide ▴
Sources
cspec ↗
PP2 VCEPATM HBOP VCEP does not permit use of PP2; ATM does not have a defined low rate of benign missense variation. Details ▾Hide ▴
Sources
cspec ↗
PP4 VCEPATM HBOP VCEP does not permit use of PP4 due to genetic heterogeneity of breast cancer and because A-T phenotype evidence is built into the PM3/BP2 table. Details ▾Hide ▴
Sources
cspec ↗
PP5 VCEPPP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee for the ATM HBOP VCEP. Details ▾Hide ▴
Sources
cspec ↗
BS2 VCEPATM HBOP VCEP does not permit use of BS2; ATM has incomplete penetrance. Details ▾Hide ▴
Sources
cspec ↗
BS4 VCEPATM HBOP VCEP does not permit use of BS4; co-segregation analysis in low-penetrance genes can lead to false positive results for AD conditions, and informative instances of lack of co-segregation in A-T families are too rare. Details ▾Hide ▴
Sources
cspec ↗
BP1 VCEPATM HBOP VCEP does not permit use of BP1; missense pathogenic variants are known for ATM. Details ▾Hide ▴
Sources
cspec ↗
BP5 VCEPATM HBOP VCEP does not permit use of BP5; cases with multiple pathogenic variants have been observed in ATM with no noticeable difference in phenotype. Details ▾Hide ▴
Sources
cspec ↗
BP6 VCEPBP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee for the ATM HBOP VCEP. Details ▾Hide ▴
Sources
cspec ↗
PS5 N/APS5 is not defined in the ATM HBOP VCEP criteria set and is not used in this framework. Details ▾Hide ▴
Sources
cspec ↗

Identifiers

Gene
ATM
Transcript
NM_000051.4
Coding (HGVS c.)
NM_000051.4:c.7927+13T>A
Protein (HGVS p.)
NP_000042.3:p.?
GRCh38
chr11:108332913 T>A
GRCh37
chr11:108203640 T>A
ClinVar
386267
COSMIC
COSV53773587

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 12 / 1,609,596 alleles AF 7.46e-06 · 0 homozygotes · FAF 5.01e-06
gnomAD v2.1 2 / 248,426 alleles AF 8.05e-06 · 0 homozygotes · FAF 2.94e-06
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 7.5e-06 · 12 / 1,609,596 alleles · 0 hom · FAF 5e-06
African/African American1 / 74,978 1.3e-05
European (non-Finnish)11 / 1,178,520 9.3e-06
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 8.1e-06 · 2 / 248,426 alleles · 0 hom · FAF 2.9e-06
European (non-Finnish)2 / 113,122 1.8e-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= 7.45529e-06; MAF= 0.00075%, 12/1609596 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 1.33372e-05; MAF= 0.00133%, 1/74978 alleles, homozygotes = 0); grpmax FAF= 5.01e-06.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 8.05069e-06; MAF= 0.00081%, 2/248426 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.768e-05; MAF= 0.00177%, 2/113122 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -151 bp
0.030
SpliceAI acceptor gainat -377 bp
0.000
SpliceAI donor lossat -13 bp
0.010
SpliceAI donor gainat -92 bp
0.000
Pangolin splice lossmagnitude shown
-0.040
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingSpliceAI predicts no splicing impact for c.7927+13T>A (max delta score = 0.03). This is ≤0.1, meeting the ATM HBOP VCEP BP4 threshold for no predicted splicing impact. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.03 (≤0.1 threshold)
Sources
spliceai ↗cspec ↗
BP7 Supportingc.7927+13T>A is an intronic variant at the donor +13 position, which is further than (but not including) +7. This meets the ATM HBOP VCEP BP7 definition for deep intronic variants unlikely to affect splicing. Details ▾Hide ▴
Evidence considered
  • Variant located at donor +13
  • beyond the +7 deep intronic threshold
Sources
cspec ↗
PP3 SpliceAI predicts no significant splicing impact (max delta score = 0.03). The ATM HBOP VCEP PP3 threshold for splicing variants is SpliceAI ≥0.2, which is not met. No other computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.03 (<0.2 threshold)
Sources
spliceai ↗cspec ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).

7 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

  • 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.
    Richards S et al. · 2015
    Standards and guidelines for the interpretation of sequence variants (ACMG/AMP 2015). Provides the generic criteria combination framework but does not discuss NM_000051.4:c.7927+13T>A.
    Does not name this variant
    PMID 25741868 ↗
  • Hereditary Ataxia Overview.
    Adam MP et al. · 1993
    Hereditary Ataxia Overview (GeneReviews). Provides general clinical background on hereditary ataxias including ataxia telangiectasia. NM_000051.4:c.7927+13T>A was not identified in this review.
    Does not name this variant
    PMID 20301317 ↗
  • Ataxia-Telangiectasia.
    Adam MP et al. · 1993
    Ataxia-Telangiectasia (GeneReviews). Provides clinical description of A-T. NM_000051.4:c.7927+13T>A was not identified in this review.
    Does not name this variant
    PMID 20301790 ↗
  • EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood.
    van de Warrenburg BP et al. · 2014
    EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. Provides diagnostic guidelines for hereditary ataxias including ataxia telangiectasia. NM_000051.4:c.7927+13T>A was not identified in this guideline.
    Does not name this variant
    PMID 24418350 ↗
  • 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. · 2015
    ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. General guideline; NM_000051.4:c.7927+13T>A was not identified.
    Does not name this variant
    PMID 25394175 ↗
  • EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.
    Gasser T et al. · 2010
    EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. General diagnostic guideline; NM_000051.4:c.7927+13T>A was not identified.
    Does not name this variant
    PMID 20050888 ↗
  • Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
    Nykamp K et al. · 2017
    Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. General classification framework; NM_000051.4:c.7927+13T>A was not identified.
    Does not name this variant
    PMID 28492532 ↗

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

gnomAD v4.1 12 / 1,609,596 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.030 Open source ↗
ClinVar Captured ClinVar source record Open source ↗
COSMIC Captured COSMIC 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= 7.45529e-06; MAF= 0.00075%, 12/1609596 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 1.33372e-05; MAF= 0.00133%, 1/74978 alleles, homozygotes = 0); grpmax FAF= 5.01e-06.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 8.05069e-06; MAF= 0.00081%, 2/248426 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.768e-05; MAF= 0.00177%, 2/113122 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant is present in ClinVar (Variation ID: 386267); submission details unavailable.

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).

Somatic

This variant has previously been reported in somatic cancers (COSMIC; COSV53773587, n = 1 times).