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NM_006231.4(POLE):c.4307G>A (p.Arg1436Gln) AND Colorectal cancer, susceptibility to, 12

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 29, 2021
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:
RCV000544678.11

Allele description [Variation Report for NM_006231.4(POLE):c.4307G>A (p.Arg1436Gln)]

NM_006231.4(POLE):c.4307G>A (p.Arg1436Gln)

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.4307G>A (p.Arg1436Gln)
HGVS:
  • NC_000012.12:g.132643544C>T
  • NG_033840.1:g.48981G>A
  • NM_006231.4:c.4307G>AMANE SELECT
  • NP_006222.2:p.Arg1436Gln
  • NP_006222.2:p.Arg1436Gln
  • LRG_789t1:c.4307G>A
  • LRG_789:g.48981G>A
  • LRG_789p1:p.Arg1436Gln
  • NC_000012.11:g.133220130C>T
  • NM_006231.2:c.4307G>A
  • NM_006231.3:c.4307G>A
Protein change:
R1436Q
Links:
dbSNP: rs754518522
NCBI 1000 Genomes Browser:
rs754518522
Molecular consequence:
  • NM_006231.4:c.4307G>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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001775503St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)
Uncertain significance
(Jul 29, 2021)
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, SCV001775503.1

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

Description

The POLE c.4307G>A (p.Arg1436Gln) missense change has a maximum subpopulation frequency of 0.020% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/12-133220130-C-T). Five of seven in silico tools predict a deleterious effect of this variant on protein function (PP3), but to our knowledge these predictions have not been confirmed by functional assays. This variant has been reported in an individual with a personal history of breast cancer diagnosed at age 48 and a family history of stomach and colon cancers (PMID: 32522261). In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PP3.

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

Last Updated: Feb 1, 2025