NM_002691.4(POLD1):c.245C>T (p.Pro82Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 23, 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:: RCV000566453.3

Allele description [Variation Report for NM_002691.4(POLD1):c.245C>T (p.Pro82Leu)]

NM_002691.4(POLD1):c.245C>T (p.Pro82Leu)

Gene:

POLD1:DNA polymerase delta 1, catalytic subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.33

Genomic location:

Preferred name:

NM_002691.4(POLD1):c.245C>T (p.Pro82Leu)

HGVS:

NC_000019.10:g.50399413C>T
NG_033800.1:g.20091C>T
NM_001256849.1:c.245C>T
NM_001308632.1:c.245C>T
NM_002691.4:c.245C>TMANE SELECT
NP_001243778.1:p.Pro82Leu
NP_001295561.1:p.Pro82Leu
NP_002682.2:p.Pro82Leu
LRG_785t1:c.245C>T
LRG_785t2:c.245C>T
LRG_785:g.20091C>T
LRG_785p1:p.Pro82Leu
LRG_785p2:p.Pro82Leu
NC_000019.9:g.50902670C>T
NM_002691.2:c.245C>T
NM_002691.3:c.245C>T
NM_002691.4:c.245C>T
NR_046402.2:n.290C>T

Protein change:

P82L

Links:

dbSNP: rs201006221

NCBI 1000 Genomes Browser:

rs201006221

Molecular consequence:

NM_001256849.1:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001308632.1:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002691.4:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_046402.2:n.290C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000670946	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Jun 24, 2015)	germline	clinical testing	Citation Link,
SCV002534636	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Apr 23, 2021)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000670946

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Jun 24, 2015)

germline

clinical testing

Citation Link,

SCV002534636

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Apr 23, 2021)

germline

curation

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

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, curation

Citations

PubMed

Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas.

Spier I, Holzapfel S, Altmüller J, Zhao B, Horpaopan S, Vogt S, Chen S, Morak M, Raeder S, Kayser K, Stienen D, Adam R, Nürnberg P, Plotz G, Holinski-Feder E, Lifton RP, Thiele H, Hoffmann P, Steinke V, Aretz S.

Int J Cancer. 2015 Jul 15;137(2):320-31. doi: 10.1002/ijc.29396. Epub 2015 Jan 20.

PubMed [citation]

PMID:: 25529843

Details of each submission

From Ambry Genetics, SCV000670946.4

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

Description

The p.P82L variant (also known as c.245C>T), located in coding exon 2 of the POLD1 gene, results from a C to T substitution at nucleotide position 245. The proline at codon 82 is replaced by leucine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs201006221, 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.P82L 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

From Sema4, Sema4, SCV002534636.1

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

#	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: Mar 16, 2024

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