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NM_002691.4(POLD1):c.1157G>A (p.Arg386His) AND Colorectal cancer, susceptibility to, 10

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 15, 2024
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:
RCV000233864.10

Allele description [Variation Report for NM_002691.4(POLD1):c.1157G>A (p.Arg386His)]

NM_002691.4(POLD1):c.1157G>A (p.Arg386His)

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.1157G>A (p.Arg386His)
HGVS:
  • NC_000019.10:g.50403512G>A
  • NG_033800.1:g.24190G>A
  • NM_001256849.1:c.1157G>A
  • NM_001308632.1:c.1157G>A
  • NM_002691.4:c.1157G>AMANE SELECT
  • NP_001243778.1:p.Arg386His
  • NP_001295561.1:p.Arg386His
  • NP_002682.2:p.Arg386His
  • LRG_785t1:c.1157G>A
  • LRG_785t2:c.1157G>A
  • LRG_785:g.24190G>A
  • LRG_785p1:p.Arg386His
  • LRG_785p2:p.Arg386His
  • NC_000019.9:g.50906769G>A
  • NM_002691.2:c.1157G>A
  • NM_002691.3:c.1157G>A
  • NR_046402.2:n.1202G>A
Protein change:
R386H
Links:
dbSNP: rs764023083
NCBI 1000 Genomes Browser:
rs764023083
Molecular consequence:
  • NM_001256849.1:c.1157G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001308632.1:c.1157G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002691.4:c.1157G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046402.2:n.1202G>A - 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
SCV000287505Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 15, 2024) 		germlineclinical testing

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

SCV004203479Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 20, 2023) 		unknownclinical 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
not providedunknownunknownnot 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV000287505.8

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

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 386 of the POLD1 protein (p.Arg386His). This variant is present in population databases (rs764023083, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 239224). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLD1 protein function with a negative predictive value of 80%. 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.

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

From Baylor Genetics, SCV004203479.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024