0%
ATMc.6602T>CUncertain significance
Print report
Variant interpretation report

ATM c.6602T>C, p.Val2201Ala

NM_000051.4:c.6602T>C NP_000042.3:p.(Val2201Ala) Missense · exon 46 View identifiers
Classification
Uncertain significance

Variant description:

The ATM NM_000051.4:c.6602T>C (NP_000042.3:p.(Val2201Ala)) missense variant has not previously been reported in somatic cancers (COSMIC). Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).

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.

About ATM

ATM encodes a kinase that acts as a master controller of the cellular DNA damage response: it detects double-strand breaks and coordinates DNA repair, cell cycle arrest, or apoptosis through downstream targets including p53, BRCA1, and CHK2. Loss-of-function mutations in both copies of ATM cause ataxia telangiectasia, an autosomal recessive disorder characterized by neurological problems, immune deficiency, and cancer predisposition. ATM functions as a tumor suppressor: individuals with ataxia telangiectasia are prone to childhood lymphomas, leukemias, and breast cancer, while carriers of a single altered copy have increased risk of breast, pancreatic, prostate, and other cancers. Somatic ATM mutations also occur in lymphoid malignancies and solid tumors, and ATM-deficient cancers are often especially sensitive to DNA-damaging treatments.

NCBI Gene ↗ OncoKB ↗
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 v1.6. 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

Met at supporting: the variant is absent from gnomAD v2.1 and v4.1, corresponding to no observed allele and a frequency ≤.001%.

Benign criteria applied · 1
BP4Supporting
BP4 · supporting

Met: REVEL 0.171 is at or below the VCEP missense cutoff of ≤0.249.

Recorded classification: Uncertain significance

VUS: PM2 (supporting) and BP4 (supporting) were applied, but the ATM VCEP's criteria-combination rules did not reach a pathogenic or benign classification.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

No screenshot for this evidence
REVEL score
0.171 recorded score

Recorded REVEL score: 0.171. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 →
ClinVar submissions
4 reported laboratory submissions

4 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

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
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under ClinGen ATM VCEP v1.6, with the data and sources behind each one.

28 criteria with recorded statuses: 2 met · 3 not met · 7 not assessed · 16 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

Among the requested codon, residue, and domain criteria, PS1 is not assessed because no qualifying same-amino-acid pathogenic comparator was identified; PM1, PM5, PP2, and BP1 are not applicable under ATM VCEP v1.6.

PS2, PM6, and BS4 are not applicable under the ATM HBOP VCEP v1.6 specifications.

PP1 cannot be assessed because no qualifying affected-relative segregation data are documented.

Only PS4 is applicable under the ATM VCEP, but the available materials do not provide verified variant-specific case-control data needed to assess it.

PP4, PP5, BP5, and BP6 are not applicable under the VCEP's own criterion entries.

PP3 is not met because neither named pathogenic computational path reaches its VCEP threshold; BP4 Supporting is met through the named benign missense path; BP7 is outside the variant's missense scope.

Met · 2

PM2 SupportingVCEPMet at supporting: the variant is absent from gnomAD v2.1 and v4.1, corresponding to no observed allele and a frequency ≤.001%. Details ▾Hide ▴
Reasoning

The ATM VCEP applies PM2 at supporting strength when the frequency is ≤.001% in the gnomAD subpopulation with the highest frequency, with an exception for a singleton confined to one subpopulation. NM_000051.4:c.6602T>C is absent from the all-comers gnomAD v2.1 and v4.1 records, so the observed frequency is 0 and is below the VCEP threshold. The separately queried gnomAD v2.1 non-cancer and v3.1 non-cancer records also report absence; the VCEP does not require those subsets.

VCEP rule
Frequency **≤.001%** in gnomAD subpopulation with the highest frequency Exception: If >0.001% but n=1 in a single subpopulation (not present in any other subpopulation), that is sufficiently rare and PM2\_supporting would apply.
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 CSPEC PM2 rule: Frequency ≤.001% in gnomAD subpopulation with the highest frequency; the VCEP assigns PM2 supporting strength.
  • gnomAD v2.1 all-comers record for 11-108196066-T-C: absent; no observed allele or population frequency record returned.
  • gnomAD v4.1 all-comers record for chr11-108325339-T-C: absent; no observed allele or population frequency record returned.
  • The separately queried gnomAD v2.1 non-cancer and v3.1 non-cancer records also report absence, consistent with the all-comers result.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BP4 SupportingVCEPMet: REVEL 0.171 is at or below the VCEP missense cutoff of ≤0.249. Details ▾Hide ▴
Reasoning

The variant is missense, and the VCEP BP4 missense path requires REVEL <=0.249. The exact REVEL score is 0.171, so BP4 Supporting is met. The VCEP splicing path also gives a no-predicted-impact threshold of SpliceAI <=0.1; the maximum SpliceAI delta is 0.091, which is also below that threshold. These are alternative VCEP BP4 paths within the same criterion, not additional strength. The VCEP-indexed Sun et al. Table S1 exact row independently reports REVEL 0.171.

VCEP rule
* Missense: REVEL score **≤.249** * Splicing: No predicted impact via splicing (SpliceAI **≤0.1**).
Evidence considered
  • ATM VCEP v1.6 BP4 rule: missense REVEL <=0.249; the variant is missense (NM_000051.4:c.6602T>C, p.(Val2201Ala)).
  • Local REVEL lookup for NC_000011.9:g.108196066T>C / NM_000051.4:c.6602T>C: REVEL score 0.171, meeting the VCEP BP4 missense cutoff.
  • SpliceAI Lookup for NM_000051.4:c.6602T>C: maximum delta score 0.091, also meeting the VCEP BP4 splicing cutoff of <=0.1; this is an alternative path within BP4, not an additional strength.
  • Sun et al. 2025 Supplementary Table S1, exact row c.6602T>C / V2201A / exon_46 / Missense: REVEL 0.171; Classification Intermediate, Confidence Medium-high, DeepATM_predicted No. The row's REVEL value corroborates the named BP4 predictor.
Sources
cspec ↗revelspliceai ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗

Not met · 3 · evaluated, threshold not reached

PP3 VCEPNot met: REVEL 0.171 is below >0.7333 and SpliceAI max delta 0.091 is below ≥0.2. Details ▾Hide ▴
Reasoning

The variant is missense, so the VCEP PP3 missense path uses REVEL >0.7333; the exact REVEL score is 0.171, which does not meet that threshold. The VCEP also permits its splicing path for missense variants, requiring SpliceAI >=0.2; the maximum SpliceAI delta is 0.091 (DS_AL 0.091), which does not meet that threshold. The VCEP-indexed Sun et al. Table S1 exact row for c.6602T>C/p.V2201A reports REVEL 0.171 and was consulted as corroboration; its other predictor values were not used because they are not named by the governing PP3 rule.

VCEP rule
* Missense: REVEL **\>.7333** * Splicing: Predicted impact via splicing (SpliceAI **≥0.2**) for silent, missense/in-frame and for intronic variants outside of donor and acceptor 1,2 sites.
Evidence considered
  • ATM VCEP v1.6 PP3 rule: missense REVEL >0.7333; the variant is missense (NP_000042.3:p.(Val2201Ala)).
  • Local REVEL lookup for NC_000011.9:g.108196066T>C / NM_000051.4:c.6602T>C: REVEL score 0.171.
  • SpliceAI Lookup for NM_000051.4:c.6602T>C: DS_AG 0.02, DS_AL 0.091, DS_DG 0.0, DS_DL 0.0; maximum delta score 0.091.
  • Sun et al. 2025 Supplementary Table S1, exact row c.6602T>C / V2201A / exon_46 / Missense: CADD.phred 18.45, boostDM_score 0.08653781, EVE_scores_ASM 0.142570225809575, REVEL 0.171, AlphaMissense 0.1221, GnomAD_all_AF 0, ClinVar_classification Uncertain significance, Combined_score -0.912652605123758, Classification Intermediate, Confidence Medium-high, DeepATM_predicted No. Only the REVEL value was used for PP3 because it is the named VCEP predictor.
Sources
cspec ↗revelspliceai ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗
BA1 VCEPNot met: the variant is absent from gnomAD v2.1 and v4.1, so no Grpmax Filtering AF >.5% is present. Details ▾Hide ▴
Reasoning

The ATM VCEP defines BA1 as Grpmax Filtering AF >.5% in gnomAD. NM_000051.4:c.6602T>C (p.Val2201Ala) is absent from the all-comers gnomAD v2.1 and v4.1 records, so no allele frequency exceeds the BA1 threshold. The available non-cancer extracts also report the variant as absent, but the VCEP rule does not require a non-cancer-specific dataset.

VCEP rule
Grpmax Filtering AF **\>.5%** in gnomAD
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 CSPEC BA1 rule: Grpmax Filtering AF >.5% in gnomAD.
  • gnomAD v2.1 all-comers record for 11-108196066-T-C: absent; no population allele-frequency record returned.
  • gnomAD v4.1 all-comers record for chr11-108325339-T-C: absent; no population allele-frequency record returned.
  • The separately queried gnomAD v2.1 non-cancer and v3.1 non-cancer records also report absence; the VCEP does not specify those subsets for BA1.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BS1 VCEPNot met: the variant is absent from gnomAD v2.1 and v4.1, so no Grpmax Filtering AF >.05% is present. Details ▾Hide ▴
Reasoning

The ATM VCEP defines BS1 as Grpmax Filtering AF >.05% in gnomAD. NM_000051.4:c.6602T>C (p.Val2201Ala) is absent from the all-comers gnomAD v2.1 and v4.1 records, so no allele frequency exceeds the BS1 threshold. The available non-cancer extracts also report the variant as absent, but the VCEP rule does not require a non-cancer-specific dataset.

VCEP rule
Grpmax Filtering AF **\>.05%** in gnomAD
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 CSPEC BS1 rule: Grpmax Filtering AF >.05% in gnomAD.
  • gnomAD v2.1 all-comers record for 11-108196066-T-C: absent; no population allele-frequency record returned.
  • gnomAD v4.1 all-comers record for chr11-108325339-T-C: absent; no population allele-frequency record returned.
  • The separately queried gnomAD v2.1 non-cancer and v3.1 non-cancer records also report absence; the VCEP does not specify those subsets for BS1.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 7 · no assessment recorded

PS1 VCEPNot assessed: no qualifying previously established pathogenic same-amino-acid comparator was identified for p.Val2201Ala; SpliceAI maximum delta was 0.091. Details ▾Hide ▴
Reasoning

The ATM VCEP defines PS1 for a missense variant as the same amino acid change as a previously established pathogenic variant, provided splicing is ruled out for both alterations. NM_000051.4:c.6602T>C is a missense variant, and SpliceAI gives a maximum delta score of 0.091 with no significant predicted splice impact. However, the governing ATM_PS1_1.6.pdf contains no entry for c.6602T>C, p.Val2201Ala, or p.V2201A, and the searched ATM VCEP full-text files contain no qualifying previously established pathogenic same-amino-acid comparator. The available evidence is therefore insufficient to assess PS1, rather than evidence that the criterion is absent.

VCEP rule
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change ... Missense: This rule may be applied only when a splice defect is ruled out for both alterations either by RNA analysis and/or in silico splice predictions
Evidence considered
  • ATM PS1 guide: PS1 is for the same amino acid change as a previously established pathogenic variant regardless of nucleotide change; the missense path requires a splice defect to be ruled out for both alterations.
  • ATM_PS1_1.6.pdf: searches for c.6602T>C, p.Val2201Ala, and p.V2201A returned no entry.
  • Suppl_TableS1_PMID 40580951, Table S1 row for chr11:108325339 T>C / c.6602T>C / V2201A: exon 46, missense, Classification Uncertain significance, Combined_score -0.912652605123758, Confidence Medium-high, DeepATM_predicted No.
  • SpliceAI result for NM_000051.4:c.6602T>C: maximum delta score 0.091 (DS_AL 0.091), with no significant predicted splice impact.
Still missing
  • ATM_PS1_1.6.pdf was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no entry for this variant was found.
  • The ATM VCEP full-text directory was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no qualifying same-amino-acid pathogenic comparator was found.
Sources
cspec ↗vcep_atm_ps1_1_6 ↗spliceai ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗
PS3 VCEPNot assessed: direct prime-editing classification was Intermediate, which the VCEP table policy assigns neither PS3 nor BS3. Details ▾Hide ▴
Reasoning

The exact Suppl_TableS1 row for c.6602T>C (p.V2201A) reports Classification=Intermediate, Confidence=Medium-high, and DeepATM_predicted=No, so this is a direct prime-editing measurement. The governing VCEP table policy states that Intermediate or NA yields neither PS3 nor BS3 from this file. The approved-assay methodology table was also searched for c.6602T>C, p.Val2201Ala, and p.V2201A; it contains no variant-specific entry and is explicitly a methodology/strength-calibration table rather than a per-variant results table. No qualifying evidence that the variant fails to rescue an ATM-specific feature or radiosensitivity was identified, so PS3 cannot be applied.

VCEP rule
Use when a variant fails to rescue an ATM specifc feature, only (e.g. phosphorylation of ATM-specific targets). Do not use for radiosensitivity-only as that is not a feature specific to ATM deficiency
Evidence considered
  • Sun et al. 2025 Supplementary Table S1, row c.6602T>C / V2201A: Classification=Intermediate; Confidence=Medium-high; DeepATM_predicted=No; the row is therefore a direct prime-editing measurement but does not qualify for PS3 under the table's Intermediate rule.
  • ClinGen HBOP ATM VCEP Supplementary Tables 1 and 2: searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no variant-specific row was found. The file describes approved assay methods and strength calibration, not variant-specific results.
  • ClinGen ATM VCEP PS3 Supporting rule: apply when a variant fails to rescue an ATM-specific feature only; radiosensitivity-only evidence is excluded.
Still missing
  • The approved functional-assay table contains no entry for c.6602T>C, p.Val2201Ala, or p.V2201A; the variant's presence in the cited Mitui 2009, Barone 2009, or Scott 2002 papers was not established.
  • No qualifying variant-specific readout showing failure to rescue an ATM-specific feature or radiosensitivity is available.
Sources
cspec ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1 ↗
PS4 VCEPNot assessed: no verified case-control counts, p-value, odds ratio, or confidence interval are available for comparison with the VCEP PS4 rule. Details ▾Hide ▴
Reasoning

The ATM VCEP requires a case-control study with p-value ≤.05 and either an odds ratio, hazard ratio, or relative risk ≥2 or a lower 95% CI ≥1.5. The literature packet's ai_classified_papers is empty. The four PS4 candidate references were screened: PMID:25394175 has a full-text extraction showing no ATM or variant-specific evidence; PMID:24418350 is a general ataxia guideline with no variant-specific case-control counts in the available abstract; PMID:20301790 and PMID:42258614 have no available abstract or machine-readable full text in this case. Therefore no case-control counts, p-value, effect estimate, or confidence interval are available to evaluate the VCEP rule, and no OR or 95% CI can be computed.

VCEP rule
Case-control studies; p-value ≤.05 **and** (Odds ratio, hazard ratio, or relative risk ≥2 **or** lower 95% CI ≥1.5).
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 PS4 rule: Case-control studies; p-value ≤.05 and (Odds ratio, hazard ratio, or relative risk ≥2 or lower 95% CI ≥1.5).
  • literature_pass.json lists PMID:20301790, PMID:24418350, PMID:25394175, and PMID:42258614 as PS4 candidates, but ai_classified_papers is empty and criterion_screened is empty.
  • paper_extracts.json for PMID:25394175 states that the paper does not mention ATM, c.6602T>C, or p.(V2201A), and provides no variant-specific clinical or population evidence.
  • The available abstract snippet for PMID:24418350 identifies a general chronic-ataxia diagnostic guideline and supplies no variant-specific case-control counts.
  • No affected/control counts, p-value, effect estimate, or confidence interval for this variant were found in the available evidence; consequently an OR and 95% CI could not be computed.
Still missing
  • Obtain and verify the abstract or full text for PMID:20301790 and PMID:42258614.
  • Obtain the full text for PMID:24418350 and verify whether the exact ATM variant is reported with affected and control counts.
  • Confirm whether any source reports NM_000051.4:c.6602T>C or p.Val2201Ala in affected and unaffected/population cohorts; if so, extract counts and compute OR with 95% CI, or extract the reported p-value and effect estimate.
Sources
cspec ↗PMID:20301790 ↗PMID:24418350 ↗PMID:25394175 ↗PMID:42258614 ↗
PM3 VCEPNot assessed: no affected A-T proband observation or phase evidence was available to assign the VCEP's per-proband PM3 points. Details ▾Hide ▴
Reasoning

The ATM VCEP v1.6 PM3 rule requires recessive-disease evidence with the variant detected in trans with a pathogenic variant, and the attached points table assigns PM3 points per unrelated A-T proband according to phenotype and phase. The case evidence contains no affected A-T proband observation, phase determination, pathogenic variant in trans, or qualifying homozygous observation for NM_000051.4:c.6602T>C (p.Val2201Ala/p.V2201A). The governing file ATM_PM3_BP2_1.6.pdf was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no entry for this variant was found, so no pre-assigned PM3 code or points can be applied.

Evidence considered
  • ATM_PM3_BP2_1.6.pdf, PM3 section: the governing rule is for recessive disorders with the variant detected in trans with a pathogenic variant; its A-T table assigns points per unrelated A-T proband by phenotype and phase.
  • ATM_PM3_BP2_1.6.pdf was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no matching variant entry was found.
  • The case evidence bundle contains no affected A-T proband, phase, pathogenic-in-trans, or qualifying homozygous observation for this variant.
Still missing
  • No entry for c.6602T>C, p.Val2201Ala, or p.V2201A was found in ATM_PM3_BP2_1.6.pdf after searching all three notations.
  • Affected A-T proband observations, phenotype classification, phase, and a pathogenic variant in trans are unavailable in the case evidence.
Sources
cspec ↗vcep_atm_pm3_bp2_1_6 ↗
PP1 VCEPNot assessed: no affected-relative genotypes or segregation count are documented to evaluate the VCEP's one-, two-, or three-relative thresholds. Details ▾Hide ▴
Reasoning

PP1 is applicable only on the VCEP's autosomal-recessive path and requires affected relatives to have both variants identified in the proband. The available case evidence contains no documented affected relatives, parental or relative genotypes, phase information, or segregation count, so the VCEP segregation thresholds cannot be evaluated.

VCEP rule
AR Condition: Affected relatives must have both variants identified in proband. ... AR Condition: Segregation in ≥3 affected relatives ... AR Condition: Segregation in 2 affected relatives ... AR Condition: Segregation in 1 affected relative
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 PP1 entry requires, for AR disease, that affected relatives have both variants identified in the proband; no qualifying affected-relative segregation data are documented.
Still missing
  • Documented affected relatives with both ATM variants identified in the proband and their segregation genotypes are required.
Sources
cspec ↗
BS3 VCEPNot assessed: direct prime-editing classification was Intermediate, which the VCEP table policy assigns neither PS3 nor BS3. Details ▾Hide ▴
Reasoning

The exact Suppl_TableS1 row for c.6602T>C (p.V2201A) reports Classification=Intermediate, Confidence=Medium-high, and DeepATM_predicted=No, so this is a direct prime-editing measurement. The governing VCEP table policy states that Intermediate or NA yields neither PS3 nor BS3 from this file. The approved-assay methodology table was also searched for c.6602T>C, p.Val2201Ala, and p.V2201A; it contains no variant-specific entry and is explicitly a methodology/strength-calibration table rather than a per-variant results table. No qualifying evidence that the variant rescues an ATM-specific feature or radiosensitivity was identified, so BS3 cannot be applied.

VCEP rule
Use when a variant rescues EITHER an ATM specifc feature OR rescues radiosensitivity.
Evidence considered
  • Sun et al. 2025 Supplementary Table S1, row c.6602T>C / V2201A: Classification=Intermediate; Confidence=Medium-high; DeepATM_predicted=No; the row is therefore a direct prime-editing measurement but does not qualify for BS3 under the table's Intermediate rule.
  • ClinGen HBOP ATM VCEP Supplementary Tables 1 and 2: searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no variant-specific row was found. The file describes approved assay methods and strength calibration, not variant-specific results.
  • ClinGen ATM VCEP BS3 Supporting rule: apply when a variant rescues either an ATM-specific feature or radiosensitivity.
Still missing
  • The approved functional-assay table contains no entry for c.6602T>C, p.Val2201Ala, or p.V2201A; the variant's presence in the cited Mitui 2009, Barone 2009, or Scott 2002 papers was not established.
  • No qualifying variant-specific readout showing rescue of an ATM-specific feature or radiosensitivity is available.
Sources
cspec ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1 ↗
BP2 VCEPNot assessed: no cis/trans observation or unaffected adult proband evidence was available to assign the VCEP's BP2 points. Details ▾Hide ▴
Reasoning

The ATM VCEP v1.6 BP2 rule concerns observation in trans with a pathogenic variant for a fully penetrant dominant disorder or in cis with a pathogenic variant in any inheritance pattern; its table assigns negative points for an unaffected non-A-T adult proband according to phase and setting. The case evidence contains no cis or trans observation, unaffected adult proband status, pathogenic or likely pathogenic partner variant, or homozygous observation for NM_000051.4:c.6602T>C (p.Val2201Ala/p.V2201A). The governing file ATM_PM3_BP2_1.6.pdf was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no entry for this variant was found, so no pre-assigned BP2 code or points can be applied.

Evidence considered
  • ATM_PM3_BP2_1.6.pdf, BP2 section: the governing rule concerns observation in trans with a pathogenic variant for a fully penetrant dominant disorder or in cis with a pathogenic variant in any inheritance pattern; its table assigns negative points per unaffected non-A-T adult proband.
  • ATM_PM3_BP2_1.6.pdf was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no matching variant entry was found.
  • The case evidence bundle contains no cis/trans, partner-variant, unaffected adult proband, or qualifying homozygous observation for this variant.
Still missing
  • No entry for c.6602T>C, p.Val2201Ala, or p.V2201A was found in ATM_PM3_BP2_1.6.pdf after searching all three notations.
  • Cis/trans status, partner-variant classification, and qualifying unaffected adult proband evidence are unavailable in the case evidence.
Sources
cspec ↗vcep_atm_pm3_bp2_1_6 ↗
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANot applicable: c.6602T>C is a missense substitution, whereas the ATM VCEP PVS1 rule applies to null variant classes such as nonsense, frameshift, splice-site, initiation-codon, or exon-deletion variants. Details ▾Hide ▴
Reasoning

PVS1 is not applicable. The variant is NM_000051.4:c.6602T>C (NP_000042.3:p.(Val2201Ala)), a missense substitution in exon 46, not one of the VCEP-defined null variant classes (nonsense, frameshift, canonical +/-1 or 2 splice site, initiation codon, or single/multi-exon deletion). The governing PVS1 decision guide was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no exact variant entry was found, so no pre-assigned PVS1 code applies.

VCEP rule
Null variant (nonsense, frameshift, canonical +/-1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function (LOF) is a known mechanism of disease
Evidence considered
  • Case normalization: NM_000051.4:c.6602T>C; NP_000042.3:p.(Val2201Ala) / p.(V2201A); consequence class missense; exon 46.
  • ATM_PVS1_1.6.pdf, PVS1 definition: the VCEP lists nonsense, frameshift, canonical +/-1 or 2 splice sites, initiation codon, and single- or multi-exon deletion as the null variant classes for PVS1.
  • ATM_PVS1_1.6.pdf was searched under c.6602T>C, p.Val2201Ala, and p.V2201A; no exact variant row was located.
Still missing
  • ATM_PVS1_1.6.pdf was searched for c.6602T>C, p.Val2201Ala, and p.V2201A; no exact variant entry was found.
Sources
cspec ↗vcep_atm_pvs1_1_6 ↗
PS2 VCEPNot applicable: the ATM VCEP excludes PS2 for AD and AR disease because informative de novo occurrences have not been observed. Details ▾Hide ▴
Reasoning

The ATM HBOP VCEP specifies that PS2 is not applicable for autosomal dominant or autosomal recessive disease because informative de novo occurrences have not been observed and de novo recessive conditions are unlikely to be informed by phase. This criterion is therefore excluded regardless of whether parental testing is available.

VCEP rule
Do not use for AD or AR disease: Informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 criterion entry for PS2: applicability is not applicable; instructions exclude use for AD or AR disease.
Sources
cspec ↗
PM1 VCEPNot applicable: the ATM VCEP v1.6 explicitly marks PM1 as Not Applicable, with no authoritative domain-table entry supplied. Details ▾Hide ▴
Reasoning

The ATM VCEP v1.6 criteria entry marks PM1 as Not Applicable. The vcep_materials.json domain_tables key is empty, so there is no authoritative ATM domain-table entry to evaluate for residue 2201.

VCEP rule
Not Applicable
Evidence considered
  • ATM VCEP v1.6 CSPEC PM1 entry: Applicability = Not Applicable.
  • vcep_materials.json domain_tables: {}.
Sources
cspec ↗
PM4 N/ANot applicable: p.Val2201Ala is a missense substitution, not a stop-loss variant, which is the only variant type named by the ATM VCEP PM4 rule. Details ▾Hide ▴
Reasoning

PM4 is not applicable. The ATM VCEP specifies PM4 for stop-loss variants, whereas this variant is a missense substitution, c.6602T>C (p.Val2201Ala), that does not alter a termination codon.

VCEP rule
Use for stop-loss variants.
Evidence considered
  • Case normalization identifies NM_000051.4:c.6602T>C as NP_000042.3:p.(Val2201Ala), consequence class missense.
  • ATM VCEP v1.6 CSPEC PM4 entry: PM4 is specified for stop-loss variants.
Sources
cspec ↗
PM5 N/ANot applicable: PM5 is restricted to specified NMD-prone truncating variants, whereas c.6602T>C is a missense substitution. Details ▾Hide ▴
Reasoning

The ATM VCEP v1.6 PM5 rule is limited to NMD-prone truncating DNA variants receiving PVS1 at Very Strong with a premature termination codon upstream of p.Leu3048, or observed NMD-prone truncating splice variants receiving PVS1(RNA) at Very Strong with high-quality RNA data. This variant is a missense substitution, so it is outside the rule's specified variant types.

VCEP rule
* DNA Variants: Apply to all NMD-prone, truncating variants receiving PVS1 (must be at VeryStrong) with premature termination codons upstream of p.Leu3048 * Splice Variants: Apply only to observed (not predicted) NMD-prone, truncating variants receiving PVS1(RNA) (must be at VeryStrong with high-quality RNA data) with premature termination codons upstream of p.Leu3048. This is not applicable for predicted splice impact without RNA data or PVS1(RNA) at reduced strength.
Evidence considered
  • ATM VCEP v1.6 PM5 rule: DNA and splice variants must be NMD-prone truncating variants meeting the specified PVS1/PVS1(RNA) and premature-termination-codon conditions.
  • Suppl_TableS1_PMID 40580951, Table S1 row for c.6602T>C / V2201A: variant type Missense.
Sources
cspec ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗
PM6 VCEPNot applicable: the ATM VCEP excludes PM6 for AD and AR disease because informative de novo occurrences have not been observed. Details ▾Hide ▴
Reasoning

The ATM HBOP VCEP specifies that PM6 is not applicable for autosomal dominant or autosomal recessive disease because informative de novo occurrences have not been observed and de novo recessive conditions are unlikely to be informed by phase. The criterion is therefore excluded irrespective of any unconfirmed de novo observation.

VCEP rule
Do not use for AD or AR disease: Informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 criterion entry for PM6: applicability is not applicable; instructions exclude use for AD or AR disease.
Sources
cspec ↗
PP2 VCEPNot applicable: the ATM VCEP v1.6 explicitly marks PP2 as Not Applicable. Details ▾Hide ▴
Reasoning

The ATM VCEP v1.6 criteria entry marks PP2 as Not Applicable.

VCEP rule
Not Applicable
Evidence considered
  • ATM VCEP v1.6 CSPEC PP2 entry: Applicability = Not Applicable.
Sources
cspec ↗
PP4 VCEPNot applicable: the ATM VCEP prohibits separate PP4 use for both hereditary breast cancer and Ataxia-Telangiectasia phenotype evidence. Details ▾Hide ▴
Reasoning

The ATM VCEP marks PP4 not applicable. For autosomal dominant disease, it says not to use PP4 because breast cancer is genetically heterogeneous and features cannot readily distinguish hereditary from sporadic causes; for autosomal recessive disease, it says not to use PP4 separately because the evidence is built into the Ataxia-Telangiectasia PM3/BP2 table.

VCEP rule
Autosomal Dominant: do not use as breast cancer is a disease with multiple genetic etiology (genetic heterogeneity) and there are no features that can readily distinguish hereditary from sporadic causes. Autosomal Recessive: do not use as a separate line of evidence. Such evidence is built into the Ataxia Telangiectasia PM3|BP2 table
Evidence considered
  • The VCEP's PP4 entry states that PP4 is not applicable for autosomal dominant breast cancer and not applicable as a separate line for autosomal recessive Ataxia-Telangiectasia.
Sources
cspec ↗
PP5 VCEPNot applicable: the ATM VCEP explicitly states that PP5 is not for use. Details ▾Hide ▴
Reasoning

The ATM VCEP explicitly marks PP5 not applicable and states that this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. No PP5 assertion is made.

VCEP rule
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Evidence considered
  • The VCEP's PP5 entry states: This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Sources
cspec ↗
BS2 VCEPNot applicable: the ATM VCEP states, "Do not use: ATM has incomplete penetrance." Details ▾Hide ▴
Reasoning

BS2 is not applicable under the ATM VCEP because the VCEP explicitly instructs: Do not use: ATM has incomplete penetrance. No healthy-adult homozygote or heterozygote observation can override that criterion-level applicability decision.

VCEP rule
Do not use: ATM has incomplete penetrance.
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 CSPEC BS2 applicability instruction: Do not use: ATM has incomplete penetrance.
Sources
cspec ↗
BS4 VCEPNot applicable: the ATM VCEP excludes BS4 because AD segregation can be falsely positive and informative AR non-segregation is too rare for weight. Details ▾Hide ▴
Reasoning

The ATM HBOP VCEP specifies that BS4 is not applicable: for the autosomal-dominant condition, segregation analysis in this low-penetrance gene can produce false-positive results, and for the autosomal-recessive condition, informative lack-of-co-segregation instances are too rare to receive weight. No BS4 evidence can therefore be assigned under this VCEP.

VCEP rule
AD Condition: Co-segregation analysis in low penetrance genes can lead to false positive results (PMID 32773770) ... AR Condition: Informative instances of lack of co-segregation in A-T families are too rare to be considered for weight at this time and can also be considered for BP2 if biallelic unaffected patients are observed in an A-T family.
Evidence considered
  • ClinGen HBOP ATM VCEP v1.6 criterion entry for BS4: AD segregation analysis in low-penetrance genes can lead to false-positive results; informative AR lack-of-co-segregation instances are too rare for weight.
Sources
cspec ↗
BP1 VCEPNot applicable: the ATM VCEP v1.6 explicitly marks BP1 as Not Applicable. Details ▾Hide ▴
Reasoning

The ATM VCEP v1.6 criteria entry marks BP1 as Not Applicable.

VCEP rule
Not Applicable
Evidence considered
  • ATM VCEP v1.6 CSPEC BP1 entry: Applicability = Not Applicable.
Sources
cspec ↗
BP3 VCEPNot applicable: the ATM VCEP v1.6 CSPEC explicitly marks BP3 as Not Applicable for this framework. Details ▾Hide ▴
Reasoning

BP3 is not applicable under the ATM VCEP v1.6 CSPEC entry, which explicitly marks BP3 as Not Applicable. The variant is also a missense substitution rather than an in-frame deletion or insertion in a repetitive region.

VCEP rule
Not Applicable
Evidence considered
  • ATM VCEP v1.6 CSPEC BP3 entry: applicability is recorded as Not Applicable.
  • Case normalization identifies NM_000051.4:c.6602T>C as a missense substitution, p.(Val2201Ala).
Sources
cspec ↗
BP5 VCEPNot applicable: the ATM VCEP prohibits BP5 because multiple pathogenic variants may coexist without a noticeable phenotype difference. Details ▾Hide ▴
Reasoning

The ATM VCEP explicitly marks BP5 not applicable and instructs: Do not use, because multiple pathogenic variants can occur without a noticeable phenotype difference and ATM's low penetrance increases such co-occurrence.

VCEP rule
Do not use: Cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype (e.g. BRCA1 and BRCA2). In addition, ATM has low penetrance and will naturally occur with other pathogenic variants more frequently due to higher tolerance/presence in the general population.
Evidence considered
  • The VCEP's BP5 instruction says not to use BP5 because cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype and ATM has low penetrance.
Sources
cspec ↗
BP6 VCEPNot applicable: the ATM VCEP explicitly states that BP6 is not for use. Details ▾Hide ▴
Reasoning

The ATM VCEP explicitly marks BP6 not applicable and states that this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. No BP6 assertion is made.

VCEP rule
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Evidence considered
  • The VCEP's BP6 entry states: This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Sources
cspec ↗
BP7 N/ANot applicable: ATM c.6602T>C is a missense substitution, not a synonymous or deep intronic variant. Details ▾Hide ▴
Reasoning

The variant is a missense substitution in exon 46. The ATM VCEP BP7 rule applies to synonymous and deep intronic variants, or to observed RNA evidence for those variant types; it does not cover this missense variant.

VCEP rule
* BP7: Use for synonymous and deep intronic variants defined as further than (but not including) +7 and further than (but not including) -21 at donor and acceptor sites, respectively. * BP7(RNA): Observed lack of aberrant RNA defect for silent substitutions and intronic variants. Variable weight applied depending on curator discretion of assay quality.
Evidence considered
  • Case variant consequence: NM_000051.4:c.6602T>C encodes NP_000042.3:p.(Val2201Ala) and is annotated as missense in exon 46.
Sources
cspec ↗

Identifiers

Gene
ATM
Transcript
NM_000051.4
Coding (HGVS c.)
NM_000051.4:c.6602T>C
Protein (HGVS p.)
NP_000042.3:p.(Val2201Ala)
GRCh38
chr11:108325339 T>C
GRCh37
chr11:108196066 T>C
Location and type
Exon 46 · missense
ClinVar
230185

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 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +52 bp
0.091
SpliceAI acceptor gainat -29 bp
0.020
SpliceAI donor lossat -350 bp
0.000
SpliceAI donor gainat -293 bp
0.000
Pangolin splice lossmagnitude shown
-0.111
Pangolin splice gain
0.140

Other predictors

REVEL
0.171
BayesDel
-0.324

How the predictions were used

BP4 SupportingVCEPMet: REVEL 0.171 is at or below the VCEP missense cutoff of ≤0.249. Details ▾Hide ▴
Reasoning

The variant is missense, and the VCEP BP4 missense path requires REVEL <=0.249. The exact REVEL score is 0.171, so BP4 Supporting is met. The VCEP splicing path also gives a no-predicted-impact threshold of SpliceAI <=0.1; the maximum SpliceAI delta is 0.091, which is also below that threshold. These are alternative VCEP BP4 paths within the same criterion, not additional strength. The VCEP-indexed Sun et al. Table S1 exact row independently reports REVEL 0.171.

VCEP rule
* Missense: REVEL score **≤.249** * Splicing: No predicted impact via splicing (SpliceAI **≤0.1**).
Evidence considered
  • ATM VCEP v1.6 BP4 rule: missense REVEL <=0.249; the variant is missense (NM_000051.4:c.6602T>C, p.(Val2201Ala)).
  • Local REVEL lookup for NC_000011.9:g.108196066T>C / NM_000051.4:c.6602T>C: REVEL score 0.171, meeting the VCEP BP4 missense cutoff.
  • SpliceAI Lookup for NM_000051.4:c.6602T>C: maximum delta score 0.091, also meeting the VCEP BP4 splicing cutoff of <=0.1; this is an alternative path within BP4, not an additional strength.
  • Sun et al. 2025 Supplementary Table S1, exact row c.6602T>C / V2201A / exon_46 / Missense: REVEL 0.171; Classification Intermediate, Confidence Medium-high, DeepATM_predicted No. The row's REVEL value corroborates the named BP4 predictor.
Sources
cspec ↗revelspliceai ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗
PP3 VCEPNot met: REVEL 0.171 is below >0.7333 and SpliceAI max delta 0.091 is below ≥0.2. Details ▾Hide ▴
Reasoning

The variant is missense, so the VCEP PP3 missense path uses REVEL >0.7333; the exact REVEL score is 0.171, which does not meet that threshold. The VCEP also permits its splicing path for missense variants, requiring SpliceAI >=0.2; the maximum SpliceAI delta is 0.091 (DS_AL 0.091), which does not meet that threshold. The VCEP-indexed Sun et al. Table S1 exact row for c.6602T>C/p.V2201A reports REVEL 0.171 and was consulted as corroboration; its other predictor values were not used because they are not named by the governing PP3 rule.

VCEP rule
* Missense: REVEL **\>.7333** * Splicing: Predicted impact via splicing (SpliceAI **≥0.2**) for silent, missense/in-frame and for intronic variants outside of donor and acceptor 1,2 sites.
Evidence considered
  • ATM VCEP v1.6 PP3 rule: missense REVEL >0.7333; the variant is missense (NP_000042.3:p.(Val2201Ala)).
  • Local REVEL lookup for NC_000011.9:g.108196066T>C / NM_000051.4:c.6602T>C: REVEL score 0.171.
  • SpliceAI Lookup for NM_000051.4:c.6602T>C: DS_AG 0.02, DS_AL 0.091, DS_DG 0.0, DS_DL 0.0; maximum delta score 0.091.
  • Sun et al. 2025 Supplementary Table S1, exact row c.6602T>C / V2201A / exon_46 / Missense: CADD.phred 18.45, boostDM_score 0.08653781, EVE_scores_ASM 0.142570225809575, REVEL 0.171, AlphaMissense 0.1221, GnomAD_all_AF 0, ClinVar_classification Uncertain significance, Combined_score -0.912652605123758, Classification Intermediate, Confidence Medium-high, DeepATM_predicted No. Only the REVEL value was used for PP3 because it is the named VCEP predictor.
Sources
cspec ↗revelspliceai ↗vcep_suppl_tables1_pmid_40580951 ↗PMID:40580951 ↗
BP7 N/ANot applicable: ATM c.6602T>C is a missense substitution, not a synonymous or deep intronic variant. Details ▾Hide ▴
Reasoning

The variant is a missense substitution in exon 46. The ATM VCEP BP7 rule applies to synonymous and deep intronic variants, or to observed RNA evidence for those variant types; it does not cover this missense variant.

VCEP rule
* BP7: Use for synonymous and deep intronic variants defined as further than (but not including) +7 and further than (but not including) -21 at donor and acceptor sites, respectively. * BP7(RNA): Observed lack of aberrant RNA defect for silent substitutions and intronic variants. Variable weight applied depending on curator discretion of assay quality.
Evidence considered
  • Case variant consequence: NM_000051.4:c.6602T>C encodes NP_000042.3:p.(Val2201Ala) and is annotated as missense in exon 46.
Sources
cspec ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.171. BayesDel score = -0.324082.

6 paper records listed. 1 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.

Cited in the classification

  • Sun et al. 2025
    The VCEP-indexed Supplementary Table S1 for Sun et al. 2025 contains the exact ATM variant row c.6602T>C / p.V2201A and reports REVEL 0.171, along with the row's functional-assessment metadata. This supplement row was directly consulted for the named REVEL value; the article's raw publication text was not required.
    → BP4 · supporting Names this variant
    PMID 40580951 ↗
    Source detail
    108325339 T C c.6602T>C V2201A exon_46 11 Missense 2201 18.45 0.08653781 0.142570225809575 0.171 0.1221 0 Uncertain significance -0.912652605123758 Intermediate Medium-high No

    Location Supplementary Table S1, exact c.6602T>C / V2201A row

    Context Sun et al. 2025 ATM SNV prime-editing/deep-learning supplementary table; the exact row is labeled Missense and reports Classification Intermediate, Confidence Medium-high, and DeepATM_predicted No.

Other 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
    No paper-specific finding is recorded.
    PMID 25741868 ↗
  • Ataxia-Telangiectasia.
    Adam MP et al. · 1993
    This source was listed as a PS4 and PP5 candidate, but no abstract, full-text text, or variant-specific extraction is available in this case, so its content cannot be verified.
    PMID 20301790 ↗
  • EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood.
    van de Warrenburg BP et al. · 2014
    This source is a general guideline on chronic ataxia diagnosis and management. The available abstract snippet does not report the ATM variant or affected-versus-control case counts, and the available case material does not include machine-readable full text for verification.
    Does not name this variant
    PMID 24418350 ↗
    Quoted passage
    The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes.

    Abstract snippet

  • 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
    This paper is a general guideline on referral indications for cancer predisposition assessment. The provided text does not mention ATM, c.6602T>C, or p.(V2201A), and provides no variant-specific functional, clinical, segregation, or population-frequency evidence.
    Does not name this variant
    PMID 25394175 ↗
  • ATM-Related Cancer Predisposition.
    Adam MP et al. · 1993
    This source was listed as a PS4 and PP5 candidate, but no abstract, full-text text, or variant-specific extraction is available in this case, so its content cannot be verified.
    PMID 42258614 ↗
  • EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.
    Gasser T et al. · 2010
    No paper-specific finding is recorded.
    PMID 20050888 ↗

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

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.091 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

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories). (ClinVarID = 230185)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.171. BayesDel score = -0.324082.

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.