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NM_002693.3(POLG):c.2021G>A (p.Gly674Asp)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(4);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Sep 30, 2021)
Last evaluated:
Dec 7, 2020
Accession:
VCV000206462.9
Variation ID:
206462
Description:
single nucleotide variant
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NM_002693.3(POLG):c.2021G>A (p.Gly674Asp)

Allele ID
202990
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q26.1
Genomic location
15: 89324156 (GRCh38) GRCh38 UCSC
15: 89867387 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_765:g.15640G>A
LRG_765t1:c.2021G>A LRG_765p1:p.Gly674Asp
NC_000015.9:g.89867387C>T
... more HGVS
Protein change
G674D
Other names
p.G674D:GGC>GAC
Canonical SPDI
NC_000015.10:89324155:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Exome Aggregation Consortium (ExAC) 0.00055
The Genome Aggregation Database (gnomAD) 0.00019
Trans-Omics for Precision Medicine (TOPMed) 0.00012
The Genome Aggregation Database (gnomAD), exomes 0.00061
Links
ClinGen: CA316585
dbSNP: rs200257554
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 criteria provided, multiple submitters, no conflicts Nov 27, 2020 RCV000633561.4
Likely benign 1 criteria provided, single submitter May 7, 2018 RCV000188510.4
Uncertain significance 1 criteria provided, single submitter Oct 13, 2017 RCV000768054.1
Uncertain significance 1 criteria provided, single submitter Dec 15, 2017 RCV000720525.1
Uncertain significance 1 criteria provided, single submitter Apr 27, 2017 RCV001121414.1
Likely benign 1 criteria provided, single submitter Dec 7, 2020 RCV001721213.1
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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
Likely benign
(Dec 07, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000242124.9
Submitted: (Sep 30, 2021)
Evidence details
Comment:
This variant is associated with the following publications: (PMID: 26557169)
Likely benign
(May 07, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000861137.1
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
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: SCV000887292.1
Submitted: (Nov 16, 2018)
Evidence details
Comment:
The NM_002693.2:c.2021G>A (NP_002684.1:p.Gly674Asp) [GRCH38: NC_000015.10:g.89324156C>T] variant in POLG gene is interpretated to be a Likely Benign based on ACMG guidelines (PMID: 25741868). This variant meets … (more)
Uncertain significance
(Oct 13, 2017)
criteria provided, single submitter
Method: clinical testing
Progressive sclerosing poliodystrophy
Mitochondrial DNA depletion syndrome 4B, MNGIE type
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1
Allele origin: germline
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000898899.1
Submitted: (Dec 12, 2018)
Evidence details
Comment:
POLG NM_002693.2 exon 11 p.Gly674Asp (c.2021G>A): This variant has not been reported in the literature but is present in 0.1% (55/30782) of South Asian individuals … (more)
Uncertain significance
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
POLG-Related Spectrum Disorders
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001280024.1
Submitted: (Feb 20, 2020)
Evidence details
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
(Dec 15, 2017)
criteria provided, single submitter
Method: clinical testing
Seizures
Allele origin: germline
Ambry Genetics
Accession: SCV000851403.2
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The p.G674D variant (also known as c.2021G>A), located in coding exon 10 of the POLG gene, results from a G to A substitution at nucleotide … (more)
Likely benign
(Nov 27, 2020)
criteria provided, single submitter
Method: clinical testing
Progressive sclerosing poliodystrophy
Allele origin: germline
Invitae
Accession: SCV000754807.4
Submitted: (Jan 07, 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
A case of mitochondrial cytopathy with exertion induced dystonia. Chandra SR Journal of pediatric neurosciences 2015 PMID: 26557169
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=POLG - - - -

Text-mined citations for rs200257554...

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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 Oct 30, 2021