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NM_002691.4(POLD1):c.2166del (p.Phe723fs) AND Colorectal cancer, susceptibility to, 10

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 10, 2019
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:
RCV000691829.8

Allele description [Variation Report for NM_002691.4(POLD1):c.2166del (p.Phe723fs)]

NM_002691.4(POLD1):c.2166del (p.Phe723fs)

Gene:
POLD1:DNA polymerase delta 1, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
19q13.33
Genomic location:
Preferred name:
NM_002691.4(POLD1):c.2166del (p.Phe723fs)
HGVS:
  • NC_000019.10:g.50413437del
  • NC_000019.9:g.50916691del
  • NG_033800.1:g.34115del
  • NM_001256849.1:c.2166del
  • NM_001308632.1:c.2244del
  • NM_002691.4:c.2166delMANE SELECT
  • NP_001243778.1:p.Phe723fs
  • NP_001295561.1:p.Phe749fs
  • NP_002682.2:p.Phe723fs
  • LRG_785t1:c.2166del
  • LRG_785t2:c.2244del
  • LRG_785:g.34115del
  • LRG_785p1:p.Phe723fs
  • LRG_785p2:p.Phe749fs
  • NC_000019.9:g.50916691del
  • NC_000019.9:g.50916691delG
  • NC_000019.9:g.50916694del
  • NM_002691.3:c.2166del
  • NM_002691.3:c.2166delG
  • NR_046402.2:n.2211del
Protein change:
F723fs
Links:
dbSNP: rs1568634881
NCBI 1000 Genomes Browser:
rs1568634881
Molecular consequence:
  • NM_001256849.1:c.2166del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001308632.1:c.2244del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_002691.4:c.2166del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_046402.2:n.2211del - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000819623Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 10, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000819623.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Missense variants that disrupt the 3'-5' exonuclease (proof-reading) activity of the POLD1 protein, while not abolishing its polymerase enzyme activity, are associated with an increased risk for colonic adenomatous polyps and colon cancer (PMID: 23263490, 23447401). Loss-of-function truncating variants, which result in an absent or severely disrupted POLD1 protein, are therefore unlikely to be associated with disease. Without further clinical and genetic evidence, however, this variant has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with POLD1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe723Serfs*5) in the POLD1 gene. It is expected to result in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024