U.S. flag

An official website of the United States government

NM_006231.4(POLE):c.6674G>A (p.Arg2225His) AND Colorectal cancer, susceptibility to, 12

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 3, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000229333.14

Allele description [Variation Report for NM_006231.4(POLE):c.6674G>A (p.Arg2225His)]

NM_006231.4(POLE):c.6674G>A (p.Arg2225His)

Gene:
POLE:DNA polymerase epsilon, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.33
Genomic location:
Preferred name:
NM_006231.4(POLE):c.6674G>A (p.Arg2225His)
HGVS:
  • NC_000012.12:g.132624978C>T
  • NG_033840.1:g.67547G>A
  • NM_006231.4:c.6674G>AMANE SELECT
  • NP_006222.2:p.Arg2225His
  • NP_006222.2:p.Arg2225His
  • LRG_789t1:c.6674G>A
  • LRG_789:g.67547G>A
  • LRG_789p1:p.Arg2225His
  • NC_000012.11:g.133201564C>T
  • NM_006231.2:c.6674G>A
  • NM_006231.3:c.6674G>A
Protein change:
R2225H
Links:
dbSNP: rs538875477
NCBI 1000 Genomes Browser:
rs538875477
Molecular consequence:
  • NM_006231.4:c.6674G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Colorectal cancer, susceptibility to, 12 (CRCS12)
Synonyms:
COLORECTAL CANCER, SUSCEPTIBILITY TO, ON CHROMOSOME 12q24
Identifiers:
MONDO: MONDO:0014038; MedGen: C3554460; Orphanet: 220460; OMIM: 615083

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002584688St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)
Uncertain significance
(Oct 3, 2022)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV002584688.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The POLE c.6674G>A (p.Arg2225His) missense change has a maximum subpopulation frequency of 0.014% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with POLE-related disease. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 13, 2025