NM_080916.3(DGUOK):c.352C>T (p.Arg118Cys) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Dec 17, 2022
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:: RCV001780931.5

Allele description

NM_080916.3(DGUOK):c.352C>T (p.Arg118Cys)

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.352C>T (p.Arg118Cys)

HGVS:

NC_000002.12:g.73946815C>T
NG_008044.1:g.24990C>T
NM_001318859.2:c.352C>T
NM_001318860.2:c.61C>T
NM_001318861.2:c.61C>T
NM_001318862.2:c.61C>T
NM_001318863.2:c.61C>T
NM_080916.1:c.352C>T
NM_080916.3:c.352C>TMANE SELECT
NM_080918.3:c.352C>T
NP_001305788.1:p.Arg118Cys
NP_001305789.1:p.Arg21Cys
NP_001305790.1:p.Arg21Cys
NP_001305791.1:p.Arg21Cys
NP_001305792.1:p.Arg21Cys
NP_550438.1:p.Arg118Cys
NP_550440.1:p.Arg118Cys
NC_000002.11:g.74173942C>T
NM_080916.2:c.352C>T
NR_134893.2:n.270C>T
NR_134894.2:n.270C>T
NR_134896.2:n.270C>T
NR_134897.2:n.356C>T
NR_134898.2:n.270C>T

Protein change:

R118C

Links:

dbSNP: rs767604650

NCBI 1000 Genomes Browser:

rs767604650

Molecular consequence:

NM_001318859.2:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318860.2:c.61C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318861.2:c.61C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318862.2:c.61C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318863.2:c.61C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080916.3:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080918.3:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_134893.2:n.270C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134894.2:n.270C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134896.2:n.270C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134897.2:n.356C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134898.2:n.270C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002024074	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 18, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004292607	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 17, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19380071, 18205204, 23141463, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002024074

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 18, 2019)

germline

clinical testing

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

SCV004292607

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 17, 2022)

germline

clinical testing

PubMed (4)
[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

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

Pediatric mitochondrial respiratory chain disorders in the Centro region of Portugal.

Diogo L, Grazina M, Garcia P, Rebelo O, Veiga MA, Cuevas J, Vilarinho L, de Almeida IT, Oliveira CR.

Pediatr Neurol. 2009 May;40(5):351-6. doi: 10.1016/j.pediatrneurol.2008.11.012.

PubMed [citation]

PMID:: 19380071

See all PubMed Citations (5)

Details of each submission

From Revvity Omics, Revvity, SCV002024074.3

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

From Invitae, SCV004292607.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg118 amino acid residue in DGUOK. Other variant(s) that disrupt this residue have been observed in individuals with DGUOK-related conditions (PMID: 19380071), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DGUOK protein function. ClinVar contains an entry for this variant (Variation ID: 1324226). This missense change has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 18205204, 23141463). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs767604650, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 118 of the DGUOK protein (p.Arg118Cys).

#	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: May 1, 2024

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