NM_002691.4(POLD1):c.1634A>G (p.Tyr545Cys) AND Colorectal cancer, susceptibility to, 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 30, 2021
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:: RCV001068109.7

Allele description [Variation Report for NM_002691.4(POLD1):c.1634A>G (p.Tyr545Cys)]

NM_002691.4(POLD1):c.1634A>G (p.Tyr545Cys)

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.1634A>G (p.Tyr545Cys)

HGVS:

NC_000019.10:g.50407122A>G
NG_033800.1:g.27800A>G
NM_001256849.1:c.1634A>G
NM_001308632.1:c.1634A>G
NM_002691.4:c.1634A>GMANE SELECT
NP_001243778.1:p.Tyr545Cys
NP_001295561.1:p.Tyr545Cys
NP_002682.2:p.Tyr545Cys
LRG_785t1:c.1634A>G
LRG_785t2:c.1634A>G
LRG_785:g.27800A>G
LRG_785p1:p.Tyr545Cys
LRG_785p2:p.Tyr545Cys
NC_000019.9:g.50910379A>G
NM_002691.2:c.1634A>G
NM_002691.3:c.1634A>G
NR_046402.2:n.1679A>G

Protein change:

Y545C

Links:

dbSNP: rs2038922326

NCBI 1000 Genomes Browser:

rs2038922326

Molecular consequence:

NM_001256849.1:c.1634A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001308632.1:c.1634A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002691.4:c.1634A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_046402.2:n.1679A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Colorectal cancer, susceptibility to, 10
Synonyms:: COLORECTAL CANCER, SUSCEPTIBILITY TO, ON CHROMOSOME 19q; Colorectal cancer 10
Identifiers:: MONDO: MONDO:0012953; MedGen: C2675481; Orphanet: 220460; OMIM: 612591

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Homologene neighbors for GEO Profiles (Select 12458362) (0)
GEO Profiles
YME1L1 YME1 like 1 ATPase [Homo sapiens]
YME1L1 YME1 like 1 ATPase [Homo sapiens]
Gene ID:10730

Gene
Gene Links for GEO Profiles (Select 12458033) (1)
Gene
Lens epithelial and lens cortical fiber cell comparison
Lens epithelial and lens cortical fiber cell comparison
Accession: GDS1327

GEO DataSets
Related DataSets for GEO Profiles (Select 12456497) (1)
GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001233199	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 30, 2021)	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

SCV001233199

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 30, 2021)

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, SCV001233199.5

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 861557). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 545 of the POLD1 protein (p.Tyr545Cys).

#	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