NM_080916.3(DGUOK):c.763_766dup (p.Phe256Ter) AND Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Mar 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000008633.15

Allele description [Variation Report for NM_080916.3(DGUOK):c.763_766dup (p.Phe256Ter)]

NM_080916.3(DGUOK):c.763_766dup (p.Phe256Ter)

Genes:

DGUOK-AS1:DGUOK antisense RNA 1 [Gene - HGNC]
DGUOK:deoxyguanosine kinase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_080916.3(DGUOK):c.763_766dup (p.Phe256Ter)

HGVS:

NC_000002.12:g.73958201_73958204dup
NG_008044.1:g.36376_36379dup
NM_001318859.2:c.481_484dup
NM_001318860.2:c.472_475dup
NM_001318861.2:c.472_475dup
NM_001318862.2:c.454_457dup
NM_001318863.2:c.454_457dup
NM_080916.3:c.763_766dupMANE SELECT
NM_080918.3:c.499_502dup
NP_001305788.1:p.Phe162Ter
NP_001305789.1:p.Phe159Ter
NP_001305790.1:p.Phe159Ter
NP_001305791.1:p.Phe153Ter
NP_001305792.1:p.Phe153Ter
NP_550438.1:p.Phe256Ter
NP_550440.1:p.Phe168Ter
NC_000002.11:g.74185326_74185327insTGAT
NC_000002.11:g.74185328_74185331dup
NM_080916.1:c.763_766dupGATT
NM_080916.2:c.763_766dupGATT
NR_104029.1:n.336_339dup
NR_104030.1:n.310_313dup
NR_134893.2:n.417_420dup
NR_134894.2:n.565_568dup
NR_134895.2:n.229_232dup
NR_134896.2:n.399_402dup
NR_134897.2:n.609_612dup
NR_134898.2:n.533_536dup

Protein change:

F153*

Links:

OMIM: 601465.0003; dbSNP: rs763706988

NCBI 1000 Genomes Browser:

rs763706988

Molecular consequence:

NR_104029.1:n.336_339dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104030.1:n.310_313dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134893.2:n.417_420dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134894.2:n.565_568dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134895.2:n.229_232dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134896.2:n.399_402dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134897.2:n.609_612dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134898.2:n.533_536dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001318859.2:c.481_484dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001318860.2:c.472_475dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001318861.2:c.472_475dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001318862.2:c.454_457dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001318863.2:c.454_457dup - nonsense - [Sequence Ontology: SO:0001587]
NM_080916.3:c.763_766dup - nonsense - [Sequence Ontology: SO:0001587]
NM_080918.3:c.499_502dup - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000028842	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001133206	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Pathogenic (Sep 26, 2019)	germline	clinical testing
SCV003807395	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 25, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004805422	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 25, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Mitochondrial DNA depletion and dGK gene mutations.

Salviati L, Sacconi S, Mancuso M, Otaegui D, Camaño P, Marina A, Rabinowitz S, Shiffman R, Thompson K, Wilson CM, Feigenbaum A, Naini AB, Hirano M, Bonilla E, DiMauro S, Vu TH.

Ann Neurol. 2002 Sep;52(3):311-7.

PubMed [citation]

PMID:: 12205643

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 OMIM, SCV000028842.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880), Salviati et al. (2002) identified a homozygous 4-bp duplication (GATT) at nucleotide 763 in the DGUOK gene, resulting in a frameshift and premature termination of the protein. The patient presented at 2 months of age with poor feeding, hypotonia, nystagmus, metabolic acidosis, hepatomegaly, and elevated liver enzymes. She died at 5 months of age. Both parents and an unaffected sister were heterozygous for the mutation.

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

From Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV001133206.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV003807395.2

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

Description

ACMG classification criteria: PVS1 strong, PS4 moderated, PM2 moderated, PM3 moderated

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004805422.2

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

#	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: Nov 3, 2024

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