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NM_002693.3(POLG):c.3139C>T (p.Arg1047Trp) AND Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 3, 2022
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:
RCV001808470.8

Allele description [Variation Report for NM_002693.3(POLG):c.3139C>T (p.Arg1047Trp)]

NM_002693.3(POLG):c.3139C>T (p.Arg1047Trp)

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.3139C>T (p.Arg1047Trp)
Other names:
p.R1047W:CGG>TGG
HGVS:
  • NC_000015.10:g.89319065G>A
  • NG_008218.2:g.20731C>T
  • NG_011736.1:g.80103G>A
  • NM_001126131.2:c.3139C>T
  • NM_002693.3:c.3139C>TMANE SELECT
  • NP_001119603.1:p.Arg1047Trp
  • NP_002684.1:p.Arg1047Trp
  • NP_002684.1:p.Arg1047Trp
  • LRG_765t1:c.3139C>T
  • LRG_500:g.80103G>A
  • LRG_765:g.20731C>T
  • LRG_765p1:p.Arg1047Trp
  • NC_000015.9:g.89862296G>A
  • NM_002693.2:c.3139C>T
  • p.Arg1047Trp
Protein change:
R1047W
Links:
dbSNP: rs181860632
NCBI 1000 Genomes Browser:
rs181860632
Molecular consequence:
  • NM_001126131.2:c.3139C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.3139C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 (PEOB1)
Synonyms:
Cerebellar ataxia infantile with progressive external ophthalmoplegia; Progressive external ophthalmoplegia, autosomal recessive 1
Identifiers:
MONDO: MONDO:0009783; MedGen: C4225153; Orphanet: 254886; OMIM: 258450

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0020591513billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jan 3, 2022) 		germlineclinical testing

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

PMID:18195149

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not 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 3billion, SCV002059151.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Same nucleotide change resulting in same amino acid change has been previously reported to be associated with POLG related disorder (PMID:18195149, PS1_P). A different missense change at the same codon has been reported to be associated with POLG related disorder (PMID:12707443, PM5_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.848, 3CNET: 0.788, PP3_P). A missense variant is a common mechanism associated with Progressive external ophthalmoplegia (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000046, PM2_M). . The variant has been reported to be in trans with a pathogenic variant as compound heterozygous (3billion dataset, PM3_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Nov 10, 2024