Classification rationale

In progress — classification not generated yet.

No rationale recorded.

Gene diagram · NM_006231.4 · variants mapped to exon structure

POLE NM_006231.4

Fetching transcript structure from UCSC…

Applied criteria · 0 applied · 28 assessed

Applied · 0

No criteria were applied for this variant.

Assessed · not applied

Pathogenic

PVS1

PS1

PS2

PS3

PS4

PM1

PM2

PM3

PM4

PM5

PM6

PP1

PP2

PP3

PP4

PP5

Benign

BA1

BS1

BS2

BS3

BS4

BP1

BP2

BP3

BP4

BP5

BP6

BP7

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

This variant is present in gnomAD v4.1 (AF= 0.00023874; MAF= 0.02387%, 376/1574938 alleles, homozygotes = 3) and has highest observed frequency in the African/African American population (AF= 0.00353128; MAF= 0.35313%, 262/74194 alleles, homozygotes = 2); grpmax FAF= 0.00317984.

v2.1

This variant is present in gnomAD v2.1 (AF= 0.000357224; MAF= 0.03572%, 101/282736 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00324389; MAF= 0.32439%, 81/24970 alleles, homozygotes = 0); grpmax FAF= 0.00250493.

🇨🇦 CA

Not available in gnomAD-Canada v1.0.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.024% · 376 / 1,574,938
3 hom · FAF 0.32%

African/African American 262 / 74,194	0.35% 2 hom
Middle Eastern 14 / 5,992	0.23%
Remaining individuals 40 / 61,148	0.065%
Admixed American 28 / 59,988	0.047%
South Asian 13 / 90,316	0.014% 1 hom
European (non-Finnish) 19 / 1,144,342	0.0017%

+ 4 not observed (European (Finnish), Amish, East Asian, Ashkenazi Jewish)

gnomAD v2.1

0.036% · 101 / 282,736
0 hom · FAF 0.25%

African/African American 81 / 24,970	0.32%
Remaining individuals 4 / 7,222	0.055%
Admixed American 11 / 35,434	0.031%
South Asian 2 / 30,614	0.0065%
European (non-Finnish) 3 / 129,086	0.0023%

+ 3 not observed (Ashkenazi Jewish, East Asian, European (Finnish))

gnomAD Canada 🇨🇦

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗ gnomAD 🇨🇦 ↗

ClinVar

In progress — evidence not uploaded yet.

ClinVar ↗

In silico

In progress — evidence not uploaded yet.

SpliceAI ↗

Functional

In progress — evidence not uploaded yet.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

In progress — evidence not uploaded yet.

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Sources & reference links

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

gnomAD-Canada

SpliceAI

OncoKB

COSMIC

Triaged references · 6 PMIDs not cited in assessment

25394175 ↗ A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. CLINVAR

25741868 ↗ Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. CLINVAR

26389258 ↗ PMID 26389258 CLINVAR

26389505 ↗ Genetics of Colorectal Cancer (PDQ®): Health Professional Version. CLINVAR

26467025 ↗ A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders. CLINVAR

28492532 ↗ Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. CLINVAR