NM_002693.2(POLG):c.803G>C (p.Gly268Ala) AND Progressive sclerosing poliodystrophy

Clinical significance:Benign (Last evaluated: Oct 1, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000233823.4

Allele description [Variation Report for NM_002693.2(POLG):c.803G>C (p.Gly268Ala)]

NM_002693.2(POLG):c.803G>C (p.Gly268Ala)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.2(POLG):c.803G>C (p.Gly268Ala)
Other names:
p.G268A:GGG>GCG
HGVS:
  • NC_000015.10:g.89330133C>G
  • NG_008218.2:g.9663G>C
  • NM_002693.2:c.803G>C
  • NP_002684.1:p.Gly268Ala
  • LRG_765t1:c.803G>C
  • LRG_765:g.9663G>C
  • LRG_765p1:p.Gly268Ala
  • NC_000015.9:g.89873364C>G
  • P54098:p.Gly268Ala
Protein change:
G268A
Links:
UniProtKB: P54098#VAR_058873; dbSNP: rs61752784
NCBI 1000 Genomes Browser:
rs61752784
Molecular consequence:
  • NM_002693.2:c.803G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Progressive sclerosing poliodystrophy (MTDPS4A)
Synonyms:
Alpers Syndrome; Mitochondrial DNA depletion syndrome 4A (Alpers type); Alpers-Huttenlocher Syndrome
Identifiers:
MedGen: C0205710; Orphanet: 726; OMIM: 203700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000287674Invitaecriteria provided, single submitter
Benign
(Dec 4, 2017)
germlineclinical testing

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

SCV000887103Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicinecriteria provided, single submitter
Benign
(Oct 1, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans.

Baruffini E, Lodi T, Dallabona C, Puglisi A, Zeviani M, Ferrero I.

Hum Mol Genet. 2006 Oct 1;15(19):2846-55. Epub 2006 Aug 29.

PubMed [citation]
PMID:
16940310
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000287674.4

#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 Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicine, SCV000887103.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The NM_002693.2:c.803G>C (NP_002684.1:p.Gly268Ala) [GRCH38: NC_000015.10:g.89330133C>G] variant in POLG gene is interpretated to be a Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:16940310 ; 21880868 . This variant meets the following evidence codes reported in the ACMG-guideline. BS1:The minor allele frequency of this allele is high for Mitochondrial DNA depletion syndrome 4A (Alpers type). BS2:Observation of the variant in controls is inconsistent with penetrance of Mitochondrial DNA depletion syndrome 4A (Alpers type). BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Benign.

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

Last Updated: Apr 17, 2019

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