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NM_002693.2(POLG):c.32G>A

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(6)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Sep 21, 2021)
Last evaluated:
Aug 25, 2020
Accession:
VCV000195182.10
Variation ID:
195182
Description:
single nucleotide variant
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NM_002693.3(POLG):c.32G>A (p.Gly11Asp)

Allele ID
192343
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q26.1
Genomic location
15: 89333723 (GRCh38) GRCh38 UCSC
15: 89876954 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.9:g.89876954C>T
NC_000015.10:g.89333723C>T
NG_008218.2:g.6073G>A
... more HGVS
Protein change
G11D
Other names
-
Canonical SPDI
NC_000015.10:89333722:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00016
The Genome Aggregation Database (gnomAD), exomes 0.00017
Trans-Omics for Precision Medicine (TOPMed) 0.00028
Exome Aggregation Consortium (ExAC) 0.00018
Links
dbSNP: rs765472726
ClinGen: CA302812
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 5 criteria provided, multiple submitters, no conflicts Jun 11, 2019 RCV000724132.5
Uncertain significance 1 criteria provided, single submitter Oct 31, 2018 RCV000763999.1
Uncertain significance 1 criteria provided, single submitter Apr 28, 2017 RCV001116627.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Aug 25, 2020 RCV000633544.5
Uncertain significance 1 no assertion criteria provided Jan 1, 2019 RCV001252351.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
POLG - - GRCh38
GRCh37
1350 1469

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Nov 14, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000227273.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (2)
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Sep 11, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000242213.7
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The G11D variant has also been observed in individuals with POLG-related disorders but typically reported to occur on the same chromosome (in cis) with R852C … (more)
Likely benign
(Oct 01, 2018)
criteria provided, single submitter
Method: clinical testing
Progressive sclerosing poliodystrophy
Allele origin: germline
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV000886985.1
Submitted: (Nov 16, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The NM_002693.2:c.32G>A (NP_002684.1:p.Gly11Asp) [GRCH38: NC_000015.10:g.89333723C>T] variant in POLG gene is interpretated to be a Likely Benign based on ACMG guidelines (PMID: 25741868). This variant has … (more)
Uncertain significance
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1
Progressive sclerosing poliodystrophy
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1
Mitochondrial DNA depletion syndrome 1 (MNGIE type)
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
Mitochondrial DNA depletion syndrome 4B, MNGIE type
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894950.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Uncertain significance
(Jun 11, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000614723.2
Submitted: (Sep 25, 2019)
Evidence details
Publications
PubMed (10)
Uncertain significance
(Apr 28, 2017)
criteria provided, single submitter
Method: clinical testing
POLG-Related Spectrum Disorders
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001274737.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (6)
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Uncertain significance
(Aug 25, 2020)
criteria provided, single submitter
Method: clinical testing
Progressive sclerosing poliodystrophy
Allele origin: germline
Invitae
Accession: SCV000754790.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces glycine with aspartic acid at codon 11 of the POLG protein (p.Gly11Asp). The glycine residue is weakly conserved and there is … (more)
Uncertain significance
(Jan 01, 2019)
no assertion criteria provided
Method: clinical testing
Intellectual disability
Allele origin: unknown
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV001428103.1
Submitted: (May 05, 2020)
Evidence details
Publications
PubMed (1)
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807856.1
Submitted: (Aug 24, 2021)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001968005.1
Submitted: (Sep 21, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
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 Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease. Blankenberg FG Molecular genetics and metabolism 2012 PMID: 23084792
Next-generation sequencing for mitochondrial diseases: a wide diagnostic spectrum. Vasta V Pediatrics international : official journal of the Japan Pediatric Society 2012 PMID: 22494076
Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum. Tang S Journal of medical genetics 2011 PMID: 21880868
Mitochondrial mimicry of multiple system atrophy of the cerebellar subtype. Mehta AR Movement disorders : official journal of the Movement Disorder Society 2011 PMID: 21259344
High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Calvo SE Nature genetics 2010 PMID: 20818383
Subcomplexes of mitochondrial complex V reveal mutations in mitochondrial DNA. Smet J Electrophoresis 2009 PMID: 19862739
Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children. Stewart JD Journal of medical genetics 2009 PMID: 19251978
MtDNA mutations are a common cause of severe disease phenotypes in children with Leigh syndrome. Naess K Biochimica et biophysica acta 2009 PMID: 19103152
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Wong LJ Human mutation 2008 PMID: 18546365
Depletion of mitochondrial DNA in fibroblast cultures from patients with POLG1 mutations is a consequence of catalytic mutations. Ashley N Human molecular genetics 2008 PMID: 18487244
1H MRS spectroscopy evidence of cerebellar high lactate in mitochondrial respiratory chain deficiency. Boddaert N Molecular genetics and metabolism 2008 PMID: 17950645
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=POLG - - - -

Text-mined citations for rs765472726...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 04, 2021