NM_006231.4(POLE):c.6668A>G (p.Lys2223Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 19, 2015
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:: RCV000569077.4

Allele description [Variation Report for NM_006231.4(POLE):c.6668A>G (p.Lys2223Arg)]

NM_006231.4(POLE):c.6668A>G (p.Lys2223Arg)

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.6668A>G (p.Lys2223Arg)

HGVS:

NC_000012.12:g.132624984T>C
NG_033840.1:g.67541A>G
NM_006231.4:c.6668A>GMANE SELECT
NP_006222.2:p.Lys2223Arg
NP_006222.2:p.Lys2223Arg
LRG_789t1:c.6668A>G
LRG_789:g.67541A>G
LRG_789p1:p.Lys2223Arg
NC_000012.11:g.133201570T>C
NM_006231.2:c.6668A>G
NM_006231.3:c.6668A>G

Protein change:

K2223R

Links:

dbSNP: rs367970442

NCBI 1000 Genomes Browser:

rs367970442

Molecular consequence:

NM_006231.4:c.6668A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000671399	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Jun 19, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000671399

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Jun 19, 2015)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV000671399.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

The p.K2223R variant (also known as c.6668A>G), located in coding exon 48 of the POLE gene, results from an A to G substitution at nucleotide position 6668. The lysine at codon 2223 is replaced by arginine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs367970442, but was absent from population-based cohorts in the NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project databases. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.K2223R remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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