NM_080916.3(DGUOK):c.211C>G (p.Pro71Ala) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 23, 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:: RCV000482950.4

Allele description [Variation Report for NM_080916.3(DGUOK):c.211C>G (p.Pro71Ala)]

NM_080916.3(DGUOK):c.211C>G (p.Pro71Ala)

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.211C>G (p.Pro71Ala)

HGVS:

NC_000002.12:g.73938978C>G
NG_008044.1:g.17153C>G
NM_001318859.2:c.211C>G
NM_001318860.2:c.-36-7741C>G
NM_001318861.2:c.-37+6295C>G
NM_001318862.2:c.-37+6295C>G
NM_001318863.2:c.-36-7741C>G
NM_080916.3:c.211C>GMANE SELECT
NM_080918.3:c.211C>G
NP_001305788.1:p.Pro71Ala
NP_550438.1:p.Pro71Ala
NP_550440.1:p.Pro71Ala
NC_000002.11:g.74166105C>G
NM_080916.1:c.211C>G
NM_080916.2:c.211C>G

Protein change:

P71A

Links:

dbSNP: rs184770596

NCBI 1000 Genomes Browser:

rs184770596

Molecular consequence:

NM_001318860.2:c.-36-7741C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001318861.2:c.-37+6295C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001318862.2:c.-37+6295C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001318863.2:c.-36-7741C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001318859.2:c.211C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080916.3:c.211C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080918.3:c.211C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

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
SCV000564933	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Oct 19, 2017)	germline	clinical testing	Citation Link,
SCV004021271	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jun 23, 2023)	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

SCV000564933

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Oct 19, 2017)

germline

clinical testing

Citation Link,

SCV004021271

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jun 23, 2023)

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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical whole exome sequencing in child neurology practice.

Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A.

Ann Neurol. 2014 Oct;76(4):473-83. doi: 10.1002/ana.24251. Epub 2014 Aug 30.

PubMed [citation]

PMID:: 25131622

Details of each submission

From GeneDx, SCV000564933.3

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

Description

The P71A variant in the DGUOK gene has been reported in the homozygous state in an individual with intellectual disability and spastic quadriplegia, but the publication does not comment on the presence or absence of liver disease (Srivastava et al., 2014). The P71A variant is observed in 65/22564 (0.56%) alleles, although not in the homozygous state, from individuals of Latino background in the ExAC dataset (Lek et al., 2016). The P71A variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P71A as a variant of uncertain significance.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004021271.1

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

Description

Variant summary: DGUOK c.211C>G (p.Pro71Ala) results in a non-conservative amino acid change located in the Deoxynucleoside kinase domain (IPR031314) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 251464 control chromosomes, predominantly at a frequency of 0.0046 within the Latino subpopulation in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in DGUOK causing DGUOK-Related Disorders, allowing no conclusion about variant significance. c.211C>G has been reported in the literature in at least one homozygous individual affected with Mitochondrial DNA depletion syndrome, 3 (example: Srivastava_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 25131622). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain 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 13, 2024

ClinVar

Relating variation to medicine