NM_002691.4(POLD1):c.1561C>T (p.Arg521Trp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 12, 2023
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:: RCV001012187.5

Allele description [Variation Report for NM_002691.4(POLD1):c.1561C>T (p.Arg521Trp)]

NM_002691.4(POLD1):c.1561C>T (p.Arg521Trp)

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.1561C>T (p.Arg521Trp)

HGVS:

NC_000019.10:g.50407049C>T
NG_033800.1:g.27727C>T
NM_001256849.1:c.1561C>T
NM_001308632.1:c.1561C>T
NM_002691.4:c.1561C>TMANE SELECT
NP_001243778.1:p.Arg521Trp
NP_001295561.1:p.Arg521Trp
NP_002682.2:p.Arg521Trp
LRG_785t1:c.1561C>T
LRG_785t2:c.1561C>T
LRG_785:g.27727C>T
LRG_785p1:p.Arg521Trp
LRG_785p2:p.Arg521Trp
NC_000019.9:g.50910306C>T
NM_002691.2:c.1561C>T
NM_002691.3:c.1561C>T
NR_046402.2:n.1606C>T

Protein change:

R521W

Links:

dbSNP: rs1341055535

NCBI 1000 Genomes Browser:

rs1341055535

Molecular consequence:

NM_001256849.1:c.1561C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001308632.1:c.1561C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002691.4:c.1561C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_046402.2:n.1606C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001172610	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 12, 2023)	germline	clinical testing	Citation Link,
SCV002534593	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Nov 5, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001172610

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 12, 2023)

germline

clinical testing

Citation Link,

SCV002534593

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Nov 5, 2021)

germline

curation

Citation Link

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, curation

Details of each submission

From Ambry Genetics, SCV001172610.4

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

Description

The p.R521W variant (also known as c.1561C>T), located in coding exon 12 of the POLD1 gene, results from a C to T substitution at nucleotide position 1561. The arginine at codon 521 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

From Sema4, Sema4, SCV002534593.1

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

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine