NM_002693.2(POLG):c.1636C>T (p.Arg546Cys) 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:
RCV000473794.3

Allele description [Variation Report for NM_002693.2(POLG):c.1636C>T (p.Arg546Cys)]

NM_002693.2(POLG):c.1636C>T (p.Arg546Cys)

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.1636C>T (p.Arg546Cys)
Other names:
p.R546C:CGC>TGC; NM_001126131.1(POLG):c.1636C>T(p.Arg546Cys); NM_002693.2(POLG):c.1636C>T(p.Arg546Cys)
HGVS:
  • NC_000015.10:g.89326688G>A
  • NG_008218.2:g.13108C>T
  • NM_002693.2:c.1636C>T
  • NP_002684.1:p.Arg546Cys
  • LRG_765t1:c.1636C>T
  • LRG_765:g.13108C>T
  • LRG_765p1:p.Arg546Cys
  • NC_000015.9:g.89869919G>A
  • NG_008218.1:g.13108C>T
  • P54098:p.Arg546Cys
Protein change:
R546C
Links:
UniProtKB: P54098#VAR_014906; dbSNP: rs2307447
NCBI 1000 Genomes Browser:
rs2307447
Molecular consequence:
  • NM_002693.2:c.1636C>T - 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
SCV000556221Invitaecriteria provided, single submitter
Benign
(Dec 20, 2017)
germlineclinical testing

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

SCV000887273Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicinecriteria provided, single submitter
Benign
(Oct 1, 2018)
germlineclinical testing

PubMed (2)
[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

Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis.

Singh KK, Ayyasamy V, Owens KM, Koul MS, Vujcic M.

J Hum Genet. 2009 Sep;54(9):516-24. doi: 10.1038/jhg.2009.71. Epub 2009 Jul 24.

PubMed [citation]
PMID:
19629138
PMCID:
PMC2782392
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000556221.3

#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, SCV000887273.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The NM_002693.2:c.1636C>T (NP_002684.1:p.Arg546Cys) [GRCH38: NC_000015.10:g.89326688G>A] variant in POLG gene is interpretated to be a Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:19629138 . 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: Mar 30, 2019

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