NM_080916.3(DGUOK):c.749T>C (p.Leu250Ser) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 19, 2023
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:: RCV001564282.6

Allele description [Variation Report for NM_080916.3(DGUOK):c.749T>C (p.Leu250Ser)]

NM_080916.3(DGUOK):c.749T>C (p.Leu250Ser)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_080916.3(DGUOK):c.749T>C (p.Leu250Ser)

HGVS:

NC_000002.12:g.73958187T>C
NG_008044.1:g.36362T>C
NM_001318859.2:c.467T>C
NM_001318860.2:c.458T>C
NM_001318861.2:c.458T>C
NM_001318862.2:c.440T>C
NM_001318863.2:c.440T>C
NM_080916.3:c.749T>CMANE SELECT
NM_080918.3:c.485T>C
NP_001305788.1:p.Leu156Ser
NP_001305789.1:p.Leu153Ser
NP_001305790.1:p.Leu153Ser
NP_001305791.1:p.Leu147Ser
NP_001305792.1:p.Leu147Ser
NP_550438.1:p.Leu250Ser
NP_550440.1:p.Leu162Ser
NC_000002.11:g.74185314T>C
NM_080916.1:c.749T>C
NR_104029.1:n.352A>G
NR_104030.1:n.326A>G
NR_134893.2:n.403T>C
NR_134894.2:n.551T>C
NR_134895.2:n.215T>C
NR_134896.2:n.385T>C
NR_134897.2:n.595T>C
NR_134898.2:n.519T>C

Protein change:

L147S

Links:

dbSNP: rs749464475

NCBI 1000 Genomes Browser:

rs749464475

Molecular consequence:

NM_001318859.2:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318860.2:c.458T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318861.2:c.458T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318862.2:c.440T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318863.2:c.440T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080916.3:c.749T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080918.3:c.485T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_104029.1:n.352A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104030.1:n.326A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134893.2:n.403T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134894.2:n.551T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134895.2:n.215T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134896.2:n.385T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134897.2:n.595T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134898.2:n.519T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Platysace lanceolata maturase K (matK) gene, partial cds; chloroplast
Platysace lanceolata maturase K (matK) gene, partial cds; chloroplast
gi|308096546|gb|GQ983657.1|

Nucleotide
Bolax gummifera ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (r...
Bolax gummifera ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast gene for chloroplast product
gi|34559278|gb|AY188419.1|

Nucleotide
Aciphylla aurea ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (r...
Aciphylla aurea ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast gene for chloroplast product
gi|34559272|gb|AY188411.1|

Nucleotide
Rhytidosporum alpinum ribulose-1,5-bisphosphate carboxylase/oxygenase large subu...
Rhytidosporum alpinum ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast gene for chloroplast product
gi|33669461|gb|AY188436.1|

Nucleotide
RefSeq RNA Links for Gene (Select 361822) (3)
Nucleotide

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
SCV001787425	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 29, 2019)	germline	clinical testing	Citation Link,
SCV003524665	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16263314, 16908739, 17452231, 15639197, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001787425

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 29, 2019)

germline

clinical testing

Citation Link,

SCV003524665

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2023)

germline

clinical testing

PubMed (5)
[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	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	clinical testing

Citations

PubMed

Deoxyguanosine kinase mutations and combined deficiencies of the mitochondrial respiratory chain in patients with hepatic involvement.

Slama A, Giurgea I, Debrey D, Bridoux D, de Lonlay P, Levy P, Chretien D, Brivet M, Legrand A, Rustin P, Munnich A, Rötig A.

Mol Genet Metab. 2005 Dec;86(4):462-5. Epub 2005 Nov 2.

PubMed [citation]

PMID:: 16263314

Hepatocerebral mitochondrial DNA depletion syndrome caused by deoxyguanosine kinase (DGUOK) mutations.

Freisinger P, Fütterer N, Lankes E, Gempel K, Berger TM, Spalinger J, Hoerbe A, Schwantes C, Lindner M, Santer R, Burdelski M, Schaefer H, Setzer B, Walker UA, Horváth R.

Arch Neurol. 2006 Aug;63(8):1129-34.

PubMed [citation]

PMID:: 16908739

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV001787425.1

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

Description

Published functional studies demonstrate a damaging effect with less than 1% residual deoxyguanosine kinase activity compared to wild-type (Wang et al., 2005); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31589614, 28411097, 19265691, 26342080, 15639197, 18600543, 19125351, 18205204, 24478274, 19380071, 16263314, 17452231, 16908739, 29228108, 17280874, 22602837, 19094978, 30693370)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003524665.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This missense change has been observed in individuals with mitochondrial DNA depletion syndrome (PMID: 15639197, 16263314, 16908739, 17452231). ClinVar contains an entry for this variant (Variation ID: 488491). This variant is present in population databases (rs749464475, gnomAD 0.009%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 250 of the DGUOK protein (p.Leu250Ser). 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. Experimental studies have shown that this missense change affects DGUOK function (PMID: 15639197). For these reasons, this variant has been classified as 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: Oct 8, 2024

ClinVar

Relating variation to medicine