rs79189380

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001085411.3(NADK2):c.1104G>A(p.Pro368Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,609,028 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 11 hom., cov: 32)

Exomes 𝑓: 0.012 ( 144 hom. )

Consequence

NADK2
NM_001085411.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0910

Publications

3 publications found

Variant links:

Genes affected

NADK2 (HGNC:26404): (NAD kinase 2, mitochondrial) This gene encodes a mitochondrial kinase that catalyzes the phosphorylation of NAD to yield NADP. Mutations in this gene result in 2,4-dienoyl-CoA reductase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

NADK2 Gene-Disease associations (from GenCC):

progressive encephalopathy with leukodystrophy due to DECR deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

NADK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.042).

BP6

Variant 5-36197627-C-T is Benign according to our data. Variant chr5-36197627-C-T is described in ClinVar as Benign. ClinVar VariationId is 380573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.091 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK2	NM_001085411.3 link	c.1104G>A	p.Pro368Pro	synonymous_variant	Exon 11 of 12	ENST00000381937.9	NP_001078880.1	Q4G0N4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADK2	ENST00000381937.9 link	c.1104G>A	p.Pro368Pro	synonymous_variant	Exon 11 of 12	2	NM_001085411.3	ENSP00000371362.4		Q4G0N4-1

Frequencies

GnomAD3 genomes

AF:

0.00962

AC:

1458

AN:

151636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00441

Gnomad ASJ

AF:

0.00751

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00895

Gnomad FIN

AF:

0.00399

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00962

GnomAD2 exomes

AF:

0.00847

AC:

2097

AN:

247550

AF XY:

0.00866

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.00449

Gnomad ASJ exome

AF:

0.00709

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.00387

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00885

GnomAD4 exome

AF:

0.0121

AC:

17673

AN:

1457274

Hom.:

144

Cov.:

AF XY:

0.0120

AC XY:

8682

AN XY:

724950

show subpopulations

African (AFR)

AF:

0.00968

AC:

321

AN:

33176

American (AMR)

AF:

0.00504

AC:

222

AN:

44080

Ashkenazi Jewish (ASJ)

AF:

0.00783

AC:

203

AN:

25930

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39560

South Asian (SAS)

AF:

0.00971

AC:

832

AN:

85680

European-Finnish (FIN)

AF:

0.00431

AC:

228

AN:

52886

Middle Eastern (MID)

AF:

0.00960

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0136

AC:

15087

AN:

1110064

Other (OTH)

AF:

0.0120

AC:

724

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

794

1588

2381

3175

3969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00962

AC:

1460

AN:

151754

Hom.:

Cov.:

AF XY:

0.00942

AC XY:

698

AN XY:

74126

show subpopulations

African (AFR)

AF:

0.0109

AC:

452

AN:

41430

American (AMR)

AF:

0.00441

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00751

AC:

AN:

3460

East Asian (EAS)

AF:

0.000194

AC:

AN:

5154

South Asian (SAS)

AF:

0.00895

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00399

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0119

AC:

806

AN:

67884

Other (OTH)

AF:

0.00952

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

142

214

285

356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00993

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0126

EpiControl

AF:

0.0131

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NADK2: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Mar 07, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

NADK2-related disorder

Benign:1

Jun 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Progressive encephalopathy with leukodystrophy due to DECR deficiency

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.4

(source)

DANN

Benign

0.66

PhyloP100

-0.091

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over