U.S. flag

An official website of the United States government

NM_006231.4(POLE):c.6445C>T (p.Arg2149Cys) AND Polymerase proofreading-related adenomatous polyposis

Germline classification:
Uncertain significance (1 submission)
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003151773.4

Allele description [Variation Report for NM_006231.4(POLE):c.6445C>T (p.Arg2149Cys)]

NM_006231.4(POLE):c.6445C>T (p.Arg2149Cys)

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.6445C>T (p.Arg2149Cys)
Other names:
p.Arg2149Cys
HGVS:
  • NC_000012.12:g.132626203G>A
  • NG_033840.1:g.66322C>T
  • NM_006231.4:c.6445C>TMANE SELECT
  • NP_006222.2:p.Arg2149Cys
  • NP_006222.2:p.Arg2149Cys
  • LRG_789t1:c.6445C>T
  • LRG_789:g.66322C>T
  • LRG_789p1:p.Arg2149Cys
  • NC_000012.11:g.133202789G>A
  • NM_006231.2:c.6445C>T
  • NM_006231.3:c.6445C>T
Protein change:
R2149C
Links:
dbSNP: rs771490182
NCBI 1000 Genomes Browser:
rs771490182
Molecular consequence:
  • NM_006231.4:c.6445C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Polymerase proofreading-related adenomatous polyposis
Identifiers:
MONDO: MONDO:0018653; MedGen: C0130294

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003839158Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significancegermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

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.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV003839158.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

A heterozygous missense variation in exon 46 of the POLE gene that results in the amino acid substitution of Cystine for Arginine at codon 2149 was detected. The observed variant c.6445C>T (p.Arg2149Cys) not been reported in 1000 genomes and has MAF of 0.01% in gnomAD databases. The in silico prediction of the variant is disease causing by MutationTaster2 and CADD. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 20, 2024