POLE c.889T>C, p.Ser297Pro
NM_006231.4:c.889T>C
Likely Pathogenic
This legacy system is being phased out as Project HERA V3 is rolled out.
ACMG/AMP Criteria Applied
PS3
PM2
BP4
Genetic Information
Gene & Transcript Details
Gene
POLE
Transcript
NM_006231.4
MANE Select
Total Exons
49
Strand
Reverse (−)
Reference Sequence
NC_000012.11
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_006231.2 | Alternative | 49 exons | Reverse |
| NM_006231.3 | RefSeq Select | 49 exons | Reverse |
Variant Details
HGVS Notation
NM_006231.4:c.889T>C
Protein Change
S297P
Location
Exon 9
(Exon 9 of 49)
5'Exon Structure (49 total)3'
Functional Consequence
Missense Variant
Related Variants
No evidence of other pathogenic variants at position 297 in gene POLE
Variant interpretation based on transcript NM_006231.4
Genome Browser
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HGVS InputNM_006231:c.889T>C
Active Tracks
ConservationRefSeqClinVargnomAD
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Clinical Data
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.05%
0.1%
1%
5%
10%+
ACMG Criteria Applied
PM2
This variant is not present in gnomAD (PM2 criteria applies).
Classification
Unknown
Publications (0)
No publication details.
Clinical Statement
Functional Impact
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
No evidence of other pathogenic variants at position 297 in gene POLE
Functional Summary
Error in OpenAI Consolidation. OncoKB: POLES297PPOLES297PSomaticNCBI Gene:5426|Show additional gene information Variant OverviewPOLE, the catalytic subunit of DNA polymerase epsilon, is an enzyme involved in DNA replication and repair. Select POLE mutations lead to ultra-high mutation rates, most frequently in endometrial and colorectal cancer.The POLE S297P mutation has not specifically been reviewed by the OncoKB team. However, POLE S297F/Y are likely oncogenic, and therefore POLE S297P is considered likely oncogenic.Hide mutation effect description The POLE S297P mutation has not specifically been reviewed by the OncoKB team. However, we have mutation effect descriptions for POLE S297F/Y
JAX-CKB: No results found
Database Previews
OncoKB
JAX-CKB
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Computational Analysis
Pathogenicity Predictions
Predictor Consensus
Mixed/VUS
PP3 Applied
No
Additional Predictors
Pathogenic:
polyphen_prediction: probably_damagingprimateai: D
Benign:
CADD: 5.39metasvm: Tmetalr: T
Neutral: Show all
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PS3
PS3 (Unknown (Pre-LLM)) Strength Modified
From pre-LLM assessment (LLM Failed)
PM2
PM2 (Unknown (Pre-LLM)) Strength Modified
From pre-LLM assessment (LLM Failed)
BP4
BP4 (Unknown (Pre-LLM)) Strength Modified
From pre-LLM assessment (LLM Failed)