NM_002693.2(POLG):c.2492A>G (p.Tyr831Cys) 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:
RCV000464026.3

Allele description [Variation Report for NM_002693.2(POLG):c.2492A>G (p.Tyr831Cys)]

NM_002693.2(POLG):c.2492A>G (p.Tyr831Cys)

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.2492A>G (p.Tyr831Cys)
Other names:
p.Y831C:TAT>TGT
HGVS:
  • NC_000015.10:g.89321842T>C
  • NG_008218.2:g.17954A>G
  • NM_002693.2:c.2492A>G
  • NP_002684.1:p.Tyr831Cys
  • LRG_765t1:c.2492A>G
  • LRG_765:g.17954A>G
  • LRG_765p1:p.Tyr831Cys
  • NC_000015.9:g.89865073T>C
  • NG_008218.1:g.17954A>G
  • P54098:p.Tyr831Cys
Protein change:
Y831C; TYR831CYS
Links:
UniProtKB: P54098#VAR_023674; OMIM: 174763.0015; dbSNP: rs41549716
NCBI 1000 Genomes Browser:
rs41549716
Molecular consequence:
  • NM_002693.2:c.2492A>G - 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
SCV000556248Invitaecriteria provided, single submitter
Benign
(Jan 11, 2018)
germlineclinical testing

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

SCV000887105Wong 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

Optimization of the Y831C mutation detection in human DNA polymerase gamma by allelic discrimination assay.

Stopińska K, Grzybowski T, Malyarchuk BA, Derenko MV, Miścicka-Sliwka D.

Acta Biochim Pol. 2006;53(3):591-5. Epub 2006 Aug 23.

PubMed [citation]
PMID:
16929381
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000556248.3

#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, SCV000887105.1

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

Description

The NM_002693.2:c.2492A>G (NP_002684.1:p.Tyr831Cys) [GRCH38: NC_000015.10:g.89321842T>C] variant in POLG gene is interpretated to be a Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:16929381 ; 16943369 . 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). BP6:Reputable source(s) without shared data suggest the variant is benign. 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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