NM_002693.2(POLG):c.2152G>T (p.Ala718Ser) AND Progressive sclerosing poliodystrophy

Clinical significance:Uncertain significance (Last evaluated: Mar 14, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000529308.1

Allele description [Variation Report for NM_002693.2(POLG):c.2152G>T (p.Ala718Ser)]

NM_002693.2(POLG):c.2152G>T (p.Ala718Ser)

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.2152G>T (p.Ala718Ser)
HGVS:
  • NC_000015.10:g.89323820C>A
  • NG_008218.2:g.15976G>T
  • NM_002693.2:c.2152G>T
  • NP_002684.1:p.Ala718Ser
  • LRG_765t1:c.2152G>T
  • LRG_765:g.15976G>T
  • LRG_765p1:p.Ala718Ser
  • NC_000015.9:g.89867051C>A
Protein change:
A718S
Links:
dbSNP: rs755783536
NCBI 1000 Genomes Browser:
rs755783536
Molecular consequence:
  • NM_002693.2:c.2152G>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
SCV000630124Invitaecriteria provided, single submitter
Uncertain significance
(Mar 14, 2017)
germlineclinical testing

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

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

Details of each submission

From Invitae, SCV000630124.1

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

Description

This sequence change replaces alanine with serine at codon 718 of the POLG protein (p.Ala718Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs755783536, ExAC 0.001%) but has not been reported in the literature in individuals with a POLG-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 17, 2019

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