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NM_002691.4(POLD1):c.371T>C (p.Val124Ala) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:
Dec 29, 2018
Review status:
criteria provided, conflicting classifications
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:
RCV000657084.13

Allele description [Variation Report for NM_002691.4(POLD1):c.371T>C (p.Val124Ala)]

NM_002691.4(POLD1):c.371T>C (p.Val124Ala)

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.371T>C (p.Val124Ala)
HGVS:
  • NC_000019.10:g.50401832T>C
  • NG_033800.1:g.22510T>C
  • NM_001256849.1:c.371T>C
  • NM_001308632.1:c.371T>C
  • NM_002691.4:c.371T>CMANE SELECT
  • NP_001243778.1:p.Val124Ala
  • NP_001295561.1:p.Val124Ala
  • NP_002682.2:p.Val124Ala
  • LRG_785t1:c.371T>C
  • LRG_785t2:c.371T>C
  • LRG_785:g.22510T>C
  • LRG_785p1:p.Val124Ala
  • LRG_785p2:p.Val124Ala
  • NC_000019.9:g.50905089T>C
  • NM_002691.2:c.371T>C
  • NM_002691.3:c.371T>C
  • NR_046402.2:n.416T>C
Protein change:
V124A
Links:
dbSNP: rs199993010
NCBI 1000 Genomes Browser:
rs199993010
Molecular consequence:
  • NM_001256849.1:c.371T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001308632.1:c.371T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002691.4:c.371T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046402.2:n.416T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000568650GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))
Uncertain significance
(Dec 4, 2017)
germlineclinical testing

Citation Link,

SCV000601941Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Benign
(Dec 29, 2018)
germlineclinical testing

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

SCV001926205Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Likely benigngermlineclinical testing

SCV001974996Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Likely benigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000568650.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted POLD1 c.371T>C at the cDNA level, p.Val124Ala (V124A) at the protein level, and results in the change of a Valine to an Alanine (GTG>GCG). This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in a lung tumor (Jiang 2016). POLD1 Val124Ala was observed at an allele frequency of 0.3% (56/18,862) in individuals of East Asian ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether POLD1 Val124Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601941.3

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

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001926205.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001974996.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 23, 2024