NM_002693.2(POLG):c.1880G>A (p.Arg627Gln) AND Progressive sclerosing poliodystrophy

Clinical significance:Pathogenic (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:
RCV000660508.1

Allele description [Variation Report for NM_002693.2(POLG):c.1880G>A (p.Arg627Gln)]

NM_002693.2(POLG):c.1880G>A (p.Arg627Gln)

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.1880G>A (p.Arg627Gln)
HGVS:
  • NC_000015.10:g.89325519C>T
  • NG_008218.2:g.14277G>A
  • NM_002693.2:c.1880G>A
  • NP_002684.1:p.Arg627Gln
  • LRG_765t1:c.1880G>A
  • LRG_765:g.14277G>A
  • LRG_765p1:p.Arg627Gln
  • NC_000015.9:g.89868750C>T
Protein change:
R627Q
Links:
dbSNP: rs375305567
NCBI 1000 Genomes Browser:
rs375305567
Molecular consequence:
  • NM_002693.2:c.1880G>A - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000782608Mayo Clinic Genetic Testing Laboratories,Mayo Cliniccriteria provided, single submitter
Pathogenic
(Feb 15, 2017)
maternalclinical testing

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

SCV000886906Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicinecriteria provided, single submitter
Pathogenic
(Oct 1, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome.

Luoma PT, Luo N, Löscher WN, Farr CL, Horvath R, Wanschitz J, Kiechl S, Kaguni LS, Suomalainen A.

Hum Mol Genet. 2005 Jul 15;14(14):1907-20. Epub 2005 May 25.

PubMed [citation]
PMID:
15917273

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 Mayo Clinic Genetic Testing Laboratories,Mayo Clinic, SCV000782608.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalunknownnot providednot providednot providednot providednot providednot providednot provided

From Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicine, SCV000886906.1

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

Description

The NM_002693.2:c.1880G>A (NP_002684.1:p.Arg627Gln) [GRCH38: NC_000015.10:g.89325519C>T] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:15917273 . This variant meets the following evidence codes reported in the ACMG-guideline. PS1:This variation causes same amino-acid change as an established pathogenic variant. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 4A (Alpers type) which is a recessive disorder. PP1:This variant is co-segregated with Mitochondrial DNA depletion syndrome 4A (Alpers type) in multiple affected family members. PP2:This is a missense variant in POLG with a low rate of benign and high rate of pathogenic missense variations. PP4:Patient's phenotype or family history is highly specific for POLG. Based on the evidence criteria codes applied, the variant is suggested to be Pathogenic.

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

Last Updated: Mar 30, 2019

Support Center