NM_006231.4(POLE):c.43G>A (p.Ala15Thr) AND Colorectal cancer, susceptibility to, 12

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 12, 2022
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:: RCV000470328.9

Allele description [Variation Report for NM_006231.4(POLE):c.43G>A (p.Ala15Thr)]

NM_006231.4(POLE):c.43G>A (p.Ala15Thr)

Genes:

LOC130009266:ATAC-STARR-seq lymphoblastoid silent region 5123 [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.43G>A (p.Ala15Thr)

HGVS:

NC_000012.12:g.132687273C>T
NG_033840.1:g.5252G>A
NM_006231.4:c.43G>AMANE SELECT
NP_006222.2:p.Ala15Thr
NP_006222.2:p.Ala15Thr
LRG_789t1:c.43G>A
LRG_789:g.5252G>A
LRG_789p1:p.Ala15Thr
NC_000012.11:g.133263859C>T
NM_006231.2:c.43G>A
NM_006231.3:c.43G>A

Protein change:

A15T

Links:

dbSNP: rs1060500788

NCBI 1000 Genomes Browser:

rs1060500788

Molecular consequence:

NM_006231.4:c.43G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000543947	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 12, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000543947

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 12, 2022)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000543947.8

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 15 of the POLE protein (p.Ala15Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 405636). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 8, 2024

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