U.S. flag

An official website of the United States government

NM_002693.3(POLG):c.1880G>A (p.Arg627Gln) AND POLG-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 20, 2023
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:
RCV003985793.1

Allele description [Variation Report for NM_002693.3(POLG):c.1880G>A (p.Arg627Gln)]

NM_002693.3(POLG):c.1880G>A (p.Arg627Gln)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.3(POLG):c.1880G>A (p.Arg627Gln)
HGVS:
  • NC_000015.10:g.89325519C>T
  • NG_008218.2:g.14277G>A
  • NM_001126131.2:c.1880G>A
  • NM_002693.3:c.1880G>AMANE SELECT
  • NP_001119603.1:p.Arg627Gln
  • NP_002684.1:p.Arg627Gln
  • NP_002684.1:p.Arg627Gln
  • LRG_765t1:c.1880G>A
  • LRG_765:g.14277G>A
  • LRG_765p1:p.Arg627Gln
  • NC_000015.9:g.89868750C>T
  • NM_002693.2:c.1880G>A
Protein change:
R627Q
Links:
dbSNP: rs375305567
NCBI 1000 Genomes Browser:
rs375305567
Molecular consequence:
  • NM_001126131.2:c.1880G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.1880G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
POLG-related disorder (PEOB)
Synonyms:
POLG-related condition; POLG- Related Disorder
Identifiers:
MedGen: CN180166

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004121503PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jun 20, 2023) 		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

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 PreventionGenetics, part of Exact Sciences, SCV004121503.1

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

Description

The POLG c.1880G>A variant is predicted to result in the amino acid substitution p.Arg627Gln. This variant was reported to be causative for cerebellar ataxia syndrome, early-onset progressive external ophthalmoplegia (PEO), and sensory neuropathy when carried in trans with a second pathogenic variant (Luoma et al. 2005. PubMed ID: 15917273). A mild dominant phenotype (early-onset ptosis and gait disturbance) was present in several individuals carrying only the c.1880G>A variant. However, these symptoms were absent in at least one relative, indicating that the dominant effect of this variant may display incomplete penetrance or a variable age of onset. Additionally, the c.1880G>A variant was reported in the compound heterozygous state in an unrelated patient with sensory ataxia and focal seizures (Deschauer et al. 2007. PubMed ID: 17502560). This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org). This variant has been classified as pathogenic by several independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/436359/). Given all the evidence, we interpret POLG c.1880G>A (p.Arg627Gln) as pathogenic.

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

Last Updated: Sep 29, 2024