NM_002693.3(POLG):c.705G>A (p.Trp235Ter) AND Progressive sclerosing poliodystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 1, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000758270.1

Allele description [Variation Report for NM_002693.3(POLG):c.705G>A (p.Trp235Ter)]

NM_002693.3(POLG):c.705G>A (p.Trp235Ter)

Genes:

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
POLGARF:POLG alternative reading frame [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.705G>A (p.Trp235Ter)

HGVS:

NC_000015.10:g.89330231C>T
NG_008218.2:g.9565G>A
NM_001126131.2:c.705G>A
NM_002693.3:c.705G>AMANE SELECT
NP_001119603.1:p.Trp235Ter
NP_002684.1:p.Trp235Ter
NP_002684.1:p.Trp235Ter
LRG_765t1:c.705G>A
LRG_765:g.9565G>A
LRG_765p1:p.Trp235Ter
NC_000015.9:g.89873462C>T
NM_002693.2:c.705G>A

Protein change:

W235*

Links:

dbSNP: rs1567192879

NCBI 1000 Genomes Browser:

rs1567192879

Molecular consequence:

NM_001126131.2:c.705G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_002693.3:c.705G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Progressive sclerosing poliodystrophy (MTDPS4A)
Synonyms:: Alpers disease; Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis; Alpers progressive infantile poliodystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008758; MedGen: C0205710; Orphanet: 726; OMIM: 203700

Recent activity

Clear Turn Off Turn On

RecName: Full=Gamma-aminobutyric acid type B receptor subunit 1; Short=GABA-B re...
RecName: Full=Gamma-aminobutyric acid type B receptor subunit 1; Short=GABA-B receptor 1; Short=GABA-B-R1; Short=GABA-BR1; Short=GABABR1; Short=Gb1; Flags: Precursor
gi|12643873|sp|Q9UBS5.1|GABR1_HUMAN

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000886919	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 1, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16957900, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000886919

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 1, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations.

de Vries MC, Rodenburg RJ, Morava E, van Kaauwen EP, ter Laak H, Mullaart RA, Snoeck IN, van Hasselt PM, Harding P, van den Heuvel LP, Smeitink JA.

Eur J Pediatr. 2007 Mar;166(3):229-34. Epub 2006 Sep 7.

PubMed [citation]

PMID:: 16957900

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 Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV000886919.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The NM_002693.2:c.705G>A (NP_002684.1:p.Trp235Ter) [GRCH38: NC_000015.10:g.89330231C>T] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:16957900 . This variant meets the following evidence codes reported in the ACMG-guideline. PVS1:This variant is a predicted null variant in POLG where loss of function is a known mechanism of disease. 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. PM4:This variant causes alteration in the length of expressed protein. PP1:This variant is co-segregated with Mitochondrial DNA depletion syndrome 4A (Alpers type) in multiple affected family members. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

ClinVar

Relating variation to medicine