NM_002691.4(POLD1):c.952G>C (p.Glu318Gln) AND Colorectal cancer, susceptibility to, 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 3, 2020
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:: RCV001306412.7

Allele description [Variation Report for NM_002691.4(POLD1):c.952G>C (p.Glu318Gln)]

NM_002691.4(POLD1):c.952G>C (p.Glu318Gln)

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.952G>C (p.Glu318Gln)

HGVS:

NC_000019.10:g.50402723G>C
NG_033800.1:g.23401G>C
NM_001256849.1:c.952G>C
NM_001308632.1:c.952G>C
NM_002691.2:c.952G>C
NM_002691.4:c.952G>CMANE SELECT
NP_001243778.1:p.Glu318Gln
NP_001295561.1:p.Glu318Gln
NP_002682.2:p.Glu318Gln
LRG_785t1:c.952G>C
LRG_785t2:c.952G>C
LRG_785:g.23401G>C
LRG_785p1:p.Glu318Gln
LRG_785p2:p.Glu318Gln
NC_000019.9:g.50905980G>C
NR_046402.2:n.997G>C

Protein change:

E318Q

Links:

dbSNP: rs775232133

NCBI 1000 Genomes Browser:

rs775232133

Molecular consequence:

NM_001256849.1:c.952G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001308632.1:c.952G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002691.4:c.952G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_046402.2:n.997G>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001495784	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 3, 2020)	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

SCV001495784

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 3, 2020)

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, SCV001495784.4

#	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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POLD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 318 of the POLD1 protein (p.Glu318Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine.

#	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

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