NM_080916.3(DGUOK):c.4G>T (p.Ala2Ser) AND Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: May 28, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000660620.19

Allele description [Variation Report for NM_080916.3(DGUOK):c.4G>T (p.Ala2Ser)]

NM_080916.3(DGUOK):c.4G>T (p.Ala2Ser)

Genes:

LOC129934096:ATAC-STARR-seq lymphoblastoid active region 16036 [Gene]
DGUOK:deoxyguanosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_080916.3(DGUOK):c.4G>T (p.Ala2Ser)

Other names:

p.A2S:GCC>TCC

HGVS:

NC_000002.12:g.73926914G>T
NG_008044.1:g.5089G>T
NM_001318859.2:c.4G>T
NM_001318860.2:c.-175G>T
NM_001318861.2:c.-261G>T
NM_001318862.2:c.-261G>T
NM_001318863.2:c.-175G>T
NM_080916.3:c.4G>TMANE SELECT
NM_080918.3:c.4G>T
NP_001305788.1:p.Ala2Ser
NP_550438.1:p.Ala2Ser
NP_550440.1:p.Ala2Ser
NC_000002.11:g.74154041G>T
NM_080916.1:c.4G>T
NM_080916.2:c.4G>T
NR_134893.2:n.35G>T
NR_134894.2:n.35G>T
NR_134895.2:n.35G>T
NR_134896.2:n.35G>T
NR_134897.2:n.35G>T
NR_134898.2:n.35G>T

Protein change:

A2S

Links:

dbSNP: rs147551003

NCBI 1000 Genomes Browser:

rs147551003

Molecular consequence:

NM_001318860.2:c.-175G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318861.2:c.-261G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318862.2:c.-261G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318863.2:c.-175G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318859.2:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080916.3:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080918.3:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_134893.2:n.35G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134894.2:n.35G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134895.2:n.35G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134896.2:n.35G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134897.2:n.35G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134898.2:n.35G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
Synonyms:: Mitochondrial DNA-depletion syndrome 3, hepatocerebral; Mitochondrial DNA depletion syndrome 3; Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency
Identifiers:: MONDO: MONDO:0009636; MedGen: C5191055; Orphanet: 279934; OMIM: 251880

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000986887	GenomeConnect, ClinGen	no classification provided	not provided	unknown	phenotyping only
SCV001135900	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001297289	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000986887

GenomeConnect, ClinGen

no classification provided

not provided

unknown

phenotyping only

SCV001135900

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Benign
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV001297289

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, phenotyping only

Citations

PubMed

Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.

Mousson de Camaret B, Taanman JW, Padet S, Chassagne M, Mayençon M, Clerc-Renaud P, Mandon G, Zabot MT, Lachaux A, Bozon D.

Biochem J. 2007 Mar 1;402(2):377-85.

PubMed [citation]

PMID:: 17073823
PMCID:: PMC1798436

Details of each submission

From GenomeConnect, ClinGen, SCV000986887.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

Variant interpretted as Uncertain significance and reported on 10/30/2014 by GTR ID 320384. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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

From Mendelics, SCV001135900.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Illumina Laboratory Services, Illumina, SCV001297289.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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: Oct 8, 2024

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