0%
POLEc.6150C>AUncertain significance
Print report
Variant interpretation report

POLE c.6150C>A, p.(Phe2050Leu)

NM_006231.4:c.6150C>A NP_006222.2:p.(Phe2050Leu) View identifiers
Classification
Uncertain significance

Variant description:

No variant summary was recorded for this case.

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 POLE

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 León-Castillo et al. 2020 custom POLE framework. 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

NM_006231.4:c.6150C>A is absent from all large population databases, including gnomAD v2.1 (exomes), gnomAD v4.1 (exomes/genomes), and gnomAD-Canada v1.0. This satisfies PM2_Supporting under the generic ACMG/AMP framework (allele frequency <0.1% and absent from controls).

Benign criteria applied · 1
BP4Supporting
BP4 · supporting

Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.228 (below the 0.3 benign-leaning threshold), BayesDel score is -0.046 (negative, consistent with a benign prediction), and SpliceAI max delta score is 0.15 (below the 0.2 threshold for significant splice impact). The variant is absent from the Leon-Castillo et al. Supplementary Tables S2/S3, so the custom POLE BP4 rule is not triggered; generic ACMG/AMP BP4 applies at supporting strength based on concordant benign predictions from multiple algorithms.

Recorded classification: Uncertain significance

Only two criteria were met: PM2_Supporting (absent from gnomAD v2.1, v4.1, and gnomAD-Canada) and BP4_Supporting (concordant benign in silico predictions: REVEL 0.228, BayesDel -0.046, SpliceAI max delta 0.15). This combination of one supporting pathogenic criterion and one supporting benign criterion does not satisfy any pathogenic, likely pathogenic, likely benign, or benign combination rule under the ACMG/AMP 2015 framework. The default classification is Variant of Uncertain Significance.

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
0.150 maximum delta

Recorded SpliceAI maximum delta score: 0.150. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
ClinVar submissions
2 reported laboratory submissions

2 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. POLE, the catalytic subunit of DNA polymerase epsilon, is an enzyme involved in DNA replication and repair. Select POLE mutations lead to ultra-high m

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 León-Castillo et al. 2020 custom POLE framework, with the data and sources behind each one.

26 criteria with recorded statuses: 2 met · 22 not met · 0 not assessed · 2 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

NM_006231.4:c.6150C>A (p.Phe2050Leu) is a missense variant in the C-terminal region of POLE, far outside the exonuclease domain (residues ~268-471) where established pathogenic hotspot mutations cluster.

This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (PM2_Supporting).

Multiple lines of computational evidence (REVEL 0.228, BayesDel -0.046, SpliceAI max delta 0.15) suggest no significant impact on the gene product (BP4_Supporting).

ClinVar reports this variant as Uncertain significance (VariationID 3004425) with review status 'criteria provided, single submitter' (1-star); no expert panel classification is available.

No published functional studies, segregation analyses, de novo observations, or case-control data exist for this variant.

The variant has not been observed in COSMIC and is not listed as a recurrent variant in the Leon-Castillo et al. 2020 endometrial carcinoma cohort analysis.

With one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), the evidence is insufficient for classification; the variant remains a Variant of Uncertain Significance.

Met · 2

PM2 SupportingNM_006231.4:c.6150C>A is absent from all large population databases, including gnomAD v2.1 (exomes), gnomAD v4.1 (exomes/genomes), and gnomAD-Canada v1.0. This satisfies PM2_Supporting under the generic ACMG/AMP framework (allele frequency <0.1% and absent from controls). Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1 (0 alleles).
  • Absent from gnomAD v4.1 (0 alleles).
  • Absent from gnomAD-Canada v1.0 (0 alleles).
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.228 (below the 0.3 benign-leaning threshold), BayesDel score is -0.046 (negative, consistent with a benign prediction), and SpliceAI max delta score is 0.15 (below the 0.2 threshold for significant splice impact). The variant is absent from the Leon-Castillo et al. Supplementary Tables S2/S3, so the custom POLE BP4 rule is not triggered; generic ACMG/AMP BP4 applies at supporting strength based on concordant benign predictions from multiple algorithms. Details ▾Hide ▴
Evidence considered
  • REVEL score 0.228 — below the 0.3 benign-leaning threshold.
  • BayesDel score -0.046 — negative score
  • consistent with benign prediction.
  • SpliceAI max delta 0.15 — no significant splice impact.
Sources
revelbayesdelspliceai ↗

Not met · 22 · evaluated, threshold not reached

PS1 No known pathogenic variant at the same nucleotide position (c.6150) with the same amino acid change (p.Phe2050Leu) has been identified. ClinVar reports no pathogenic or likely pathogenic submissions for any variant at this codon. Details ▾Hide ▴
Evidence considered
  • No pathogenic variant at c.6150 with an identical amino acid change identified in ClinVar.
Sources
clinvar ↗
PS2 No de novo observation has been reported for this variant. Neither the ClinVar submissions nor the reviewed literature include a de novo report with confirmed maternity and paternity. Details ▾Hide ▴
Evidence considered
  • No de novo observation identified in available data sources.
Still missing
  • No parental testing data available.
Sources
clinvar ↗
PS3 No functional data exists for NM_006231.4:c.6150C>A (p.Phe2050Leu). The variant has not been directly tested in any published functional assay, nor does it fall within a systematically characterized range (e.g., saturation mutagenesis, CRISPR tiling screen). The position 2050 is in the C-terminal region of POLE, far outside the exonuclease domain (residues ~268-471). REVEL score of 0.228 and BayesDel score of -0.046 do not support a deleterious functional effect. The Leon-Castillo et al. 2020 supplementary tables do not include this variant. OncoKB reports no variant-specific functional evidence. Details ▾Hide ▴
Evidence considered
  • REVEL score 0.228 — below the typical pathogenic threshold of 0.5.
  • BayesDel score -0.046 — negative score consistent with benign/neutral prediction.
  • OncoKB classification: Unknown Oncogenic Effect
  • no variant-specific functional evidence curated.
  • Variant absent from Leon-Castillo et al. 2020 supplementary functional/in silico tables.
Still missing
  • No published functional studies of this variant or a systematically characterized range spanning position 2050.
Sources
revelbayesdeloncokb ↗
PS4 The variant is absent from COSMIC and was not identified in the TCGA endometrial carcinoma cohorts summarized in Leon-Castillo et al. 2020 Supplementary Table S1. The custom POLE framework requires variant-specific recurrence with a combined EC count >=10 for PS4_Supporting. The ClinVar submissions (VUS, 2 clinical laboratories) do not provide case-control or cohort evidence for PS4. Details ▾Hide ▴
Evidence considered
  • Not found in COSMIC.
  • Not listed in Leon-Castillo et al. 2020 Supplementary Table S1 (recurrent EC variants).
  • ClinVar classification is VUS with no pathogenic assertions.
Still missing
  • No published case-control or cohort data for this variant.
Sources
vcep_path_250_323_s002clinvar ↗
PM1 PM1 is not met. The variant p.Phe2050Leu is located at amino acid position 2050 in the C-terminal region of POLE, far outside the exonuclease domain (residues ~268-471) where established pathogenic hotspot missense mutations cluster (P286R, V411L, S297F, A456P, S459F). The custom POLE framework defines PM1_Strong for the five established exonuclease-domain hotspot mutations, PM1_Moderate for specific non-hotspot exonuclease-domain variants with POLE-score >=4, and PM1_Supporting for specific POLE-score 3 variants. F2050L is not in any of these lists. The variant also does not lie in a statistically significant cancer hotspot by cancerhotspots.org. No characterized functional domain encompasses position 2050. Details ▾Hide ▴
Evidence considered
  • Position 2050 is C-terminal
  • outside the exonuclease domain (residues ~268-471).
  • Not one of the five established exonuclease-domain hotspot mutations.
  • Not listed as a recurrent variant in Leon-Castillo et al. 2020 Supplementary Table S1.
  • Not a statistically significant hotspot by cancerhotspots.org.
Sources
vcep_path_250_323_s002vcep_path_250_323
PM5 No same-residue comparator variants with a pathogenic or likely pathogenic classification were identified for codon 2050. The automated PM5 candidate search returned zero same-residue candidates, and a manual ClinVar review confirms no pathogenic missense variants at p.Phe2050 with a different amino acid change. Details ▾Hide ▴
Evidence considered
  • PM5 candidate search identified 0 same-residue candidates.
  • No pathogenic/likely pathogenic ClinVar submissions at codon 2050 with a different missense change.
Sources
pm5_candidatesclinvar ↗
PM6 No de novo observation has been reported for this variant. Neither the ClinVar submissions nor the reviewed literature provide evidence of a de novo occurrence with confirmed maternity and paternity. Details ▾Hide ▴
Evidence considered
  • No de novo observation identified in available data.
Still missing
  • No parental testing data available.
Sources
clinvar ↗
PP1 No segregation data are available for this variant. No published family studies or cosegregation analyses involving NM_006231.4:c.6150C>A have been identified. Details ▾Hide ▴
Evidence considered
  • No segregation data available.
Still missing
  • No family studies or cosegregation data.
PP2 PP2 requires a low rate of benign missense variation and demonstration that missense variants are a common disease mechanism for the gene. While pathogenic POLE missense variants are well-established in the exonuclease domain (P286R, V411L, etc.), this variant lies at position 2050 in the C-terminal region, outside the exonuclease domain. No HCI prior score is available to quantify missense constraint for this gene region. Without evidence that missense variants across the full POLE protein are a common mechanism (rather than localized to the exonuclease domain), PP2 cannot be applied. Details ▾Hide ▴
Evidence considered
  • HCI prior score not available for this variant.
  • Known pathogenic POLE missense variants are concentrated in the exonuclease domain (residues ~268-471)
  • variant at position 2050 is outside this region.
Still missing
  • No gene-wide missense constraint metric available.
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score is 0.228 (below the 0.5 pathogenic threshold; in the benign-leaning range <0.3). BayesDel score is -0.046 (negative, consistent with a benign/neutral prediction). SpliceAI max delta score is 0.15 (below the 0.2 threshold for significant splice impact). The custom POLE PP3 rule requires the variant to appear in Leon-Castillo et al. 2020 Supplementary Table S2 or S3 with REVEL class 'likely disease causing' and <=1 benign in silico result; the variant is absent from both tables, so the custom rule is not triggered and generic ACMG/AMP fallback applies, which also does not support PP3. Details ▾Hide ▴
Evidence considered
  • REVEL score 0.228 — below pathogenic threshold.
  • BayesDel score -0.046 — negative
  • consistent with benign prediction.
  • SpliceAI max delta 0.15 — no significant splice impact predicted.
  • Variant absent from Leon-Castillo et al. Supplementary Tables S2 and S3.
Sources
revelbayesdelspliceai ↗vcep_path_250_323_s003vcep_path_250_323_s004
PP4 No specific phenotypic or family history data are available for this variant. The ClinVar submissions (VariationID 3004425) are classified as VUS and do not provide detailed phenotypic information. No published case reports describing the phenotype of individuals carrying this variant were identified. Details ▾Hide ▴
Evidence considered
  • No detailed phenotype or family history data available.
Still missing
  • No published clinical descriptions of carriers.
Sources
clinvar ↗
PP5 ClinVar reports this variant as Uncertain significance (VariationID 3004425) with review status 'criteria provided, single submitter' (1-star). The reviewing clinical laboratories did not classify it as pathogenic or likely pathogenic. No expert panel (3-star) classification is available, and the override rule for PP5 at 3-star expert panel does not apply at this review level. Neither of the two associated publications (PMID:25394175, PMID:28492532) mentions this specific variant. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Uncertain significance
  • 1-star review status.
  • No pathogenic or likely pathogenic submissions from any clinical laboratory.
  • Associated publications are general guideline/framework papers that do not mention this variant.
Sources
clinvar ↗PMID:25394175 ↗PMID:28492532 ↗
BA1 BA1 requires an allele frequency >1% in population databases. This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, with an observed allele frequency of 0. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 allele frequency: 0 (absent).
  • gnomAD v4.1 allele frequency: 0 (absent).
  • gnomAD-Canada allele frequency: 0 (absent).
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BS1 BS1 requires an allele frequency >0.3% in population databases. This variant is absent from all queried population databases (gnomAD v2.1, v4.1, Canada), with an observed allele frequency of 0. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 allele frequency: 0.
  • gnomAD v4.1 allele frequency: 0.
  • gnomAD-Canada allele frequency: 0.
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BS2 BS2 requires observation of the variant in a healthy adult individual for a fully penetrant disorder. This variant has not been observed in any individual in gnomAD, and no published reports describe observation in a healthy control. Details ▾Hide ▴
Evidence considered
  • Variant absent from all population databases
  • no observation in healthy individuals.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 No published functional studies have assessed NM_006231.4:c.6150C>A (p.Phe2050Leu) in a well-established assay demonstrating no deleterious effect. While REVEL (0.228) and BayesDel (-0.046) predict a benign/neutral effect, in silico predictions alone are not sufficient to satisfy BS3, which requires experimental functional data. Details ▾Hide ▴
Evidence considered
  • No experimental functional studies of this variant identified.
  • In silico predictions suggest benign effect but are insufficient for BS3.
Still missing
  • No experimental functional data for this variant.
Sources
revelbayesdel
BS4 No segregation data are available to assess non-segregation with disease. No published family studies involving this variant were identified. Details ▾Hide ▴
Evidence considered
  • No segregation or non-segregation data available.
Still missing
  • No family studies.
BP1 BP1 applies to missense variants in genes for which primarily truncating variants are known to cause disease. POLE has well-established pathogenic missense variants in the exonuclease domain (P286R, V411L, S297F, A456P, S459F) that are recognized as a pathogenic mechanism, particularly in the context of polymerase proofreading deficiency and ultramutated tumor phenotypes. Because both truncating and missense variants can be pathogenic in POLE, BP1 does not apply. Details ▾Hide ▴
Evidence considered
  • POLE has well-characterized pathogenic missense variants in the exonuclease domain.
  • Missense is a recognized disease mechanism for POLE
  • precluding BP1 application.
Sources
vcep_path_250_323
BP2 BP2 requires observation of the variant in trans with a known pathogenic variant in a gene for a fully penetrant dominant disorder, or in cis with a pathogenic variant in a recessive disorder. No such observations have been reported for this variant. Details ▾Hide ▴
Evidence considered
  • No observation in trans or cis with a pathogenic variant.
BP5 BP5 requires observation of the variant in a case with an alternative molecular cause of disease. No such observation has been reported for this variant. Details ▾Hide ▴
Evidence considered
  • No co-occurrence with an alternative molecular cause identified.
BP6 BP6 requires a reputable source to report the variant as benign. ClinVar classification is Uncertain significance with review status 'criteria provided, single submitter' (1-star). No expert panel (3-star) classification is available. The associated publications (PMID:25394175, PMID:28492532) are general guideline/framework papers that do not mention this specific variant. The PP5/BP6 3-star expert panel override rule does not apply at this review level. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Uncertain significance
  • 1-star review status.
  • No expert panel classification available.
  • Associated publications do not mention this variant.
Sources
clinvar ↗PMID:25394175 ↗PMID:28492532 ↗
PS5 No reputable source reports this variant as pathogenic. ClinVar classification is Uncertain significance with review status 'criteria provided, single submitter' (1-star). The variant has not been reported as pathogenic by an expert panel or in a peer-reviewed publication. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Uncertain significance (VariationID 3004425)
  • 2 clinical laboratories
  • review status: criteria provided
  • single submitter.
Sources
clinvar ↗
Not applicable · 2· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. NM_006231.4:c.6150C>A is a missense substitution (p.Phe2050Leu) and does not fall into the null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants as defined by the ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
  • Missense variant
  • not a predicted null variant.
Sources
pvs1_generic_framework ↗
BP7 N/ABP7 applies to synonymous (silent) variants with no predicted impact on splicing. NM_006231.4:c.6150C>A is a missense variant resulting in p.Phe2050Leu, an amino acid change. BP7 is therefore not applicable. Details ▾Hide ▴
Evidence considered
  • Missense variant with amino acid change
  • BP7 is for synonymous variants.

Identifiers

Gene
POLE
Transcript
NM_006231.4
Coding (HGVS c.)
NM_006231.4:c.6150C>A
Protein (HGVS p.)
NP_006222.2:p.(Phe2050Leu)
GRCh38
chr12:132632495 G>T
GRCh37
chr12:133209081 G>T
ClinVar
3004425

Gene diagram

Every interpreted variant in POLE, mapped onto the exon structure of NM_006231.4. Select a row to find it on the plot.

POLENM_006231.4
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

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -7 bp
0.150
SpliceAI acceptor gainat -55 bp
0.020
SpliceAI donor lossat -180 bp
0.020
SpliceAI donor gainat -7 bp
0.000
Pangolin splice lossmagnitude shown
-0.040
Pangolin splice gain
0.020

Other predictors

REVEL
0.228
BayesDel
-0.046

How the predictions were used

BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.228 (below the 0.3 benign-leaning threshold), BayesDel score is -0.046 (negative, consistent with a benign prediction), and SpliceAI max delta score is 0.15 (below the 0.2 threshold for significant splice impact). The variant is absent from the Leon-Castillo et al. Supplementary Tables S2/S3, so the custom POLE BP4 rule is not triggered; generic ACMG/AMP BP4 applies at supporting strength based on concordant benign predictions from multiple algorithms. Details ▾Hide ▴
Evidence considered
  • REVEL score 0.228 — below the 0.3 benign-leaning threshold.
  • BayesDel score -0.046 — negative score
  • consistent with benign prediction.
  • SpliceAI max delta 0.15 — no significant splice impact.
Sources
revelbayesdelspliceai ↗
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score is 0.228 (below the 0.5 pathogenic threshold; in the benign-leaning range <0.3). BayesDel score is -0.046 (negative, consistent with a benign/neutral prediction). SpliceAI max delta score is 0.15 (below the 0.2 threshold for significant splice impact). The custom POLE PP3 rule requires the variant to appear in Leon-Castillo et al. 2020 Supplementary Table S2 or S3 with REVEL class 'likely disease causing' and <=1 benign in silico result; the variant is absent from both tables, so the custom rule is not triggered and generic ACMG/AMP fallback applies, which also does not support PP3. Details ▾Hide ▴
Evidence considered
  • REVEL score 0.228 — below pathogenic threshold.
  • BayesDel score -0.046 — negative
  • consistent with benign prediction.
  • SpliceAI max delta 0.15 — no significant splice impact predicted.
  • Variant absent from Leon-Castillo et al. Supplementary Tables S2 and S3.
Sources
revelbayesdelspliceai ↗vcep_path_250_323_s003vcep_path_250_323_s004
BP7 N/ABP7 applies to synonymous (silent) variants with no predicted impact on splicing. NM_006231.4:c.6150C>A is a missense variant resulting in p.Phe2050Leu, an amino acid change. BP7 is therefore not applicable. Details ▾Hide ▴
Evidence considered
  • Missense variant with amino acid change
  • BP7 is for synonymous variants.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). REVEL score = 0.228. BayesDel score = -0.0463543.

2 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

  • 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
    Practice guideline from ACMG and NSGC presenting referral criteria for cancer predisposition assessment. NM_006231.4:c.6150C>A (p.Phe2050Leu) was not identified in this publication.
    Does not name this variant
    PMID 25394175 ↗
  • Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
    Nykamp K et al. · 2017
    Sherloc variant classification framework paper describing a refinement of ACMG-AMP criteria. NM_006231.4:c.6150C>A (p.Phe2050Leu) was not identified in this publication.
    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 Captured gnomAD v4.1 source record Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.150 Open source ↗
ClinVar 2 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 ↗

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

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories). (ClinVarID = 3004425)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). REVEL score = 0.228. BayesDel score = -0.0463543.

Functional

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. POLE, the catalytic subunit of DNA polymerase epsilon, is an enzyme involved in DNA replication and repair. Select POLE mutations lead to ultra-high m

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.