Variant rs79189380 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

NADK2 (HGNC:):

NADK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 5-36197627-C-T is Benign according to our data. Variant chr5-36197627-C-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
NADK2	NM_001085411.3 linkuse as main transcript	c.1104G>A	p.Pro368Pro	synonymous_variant	11/12	ENST00000381937.9	NP_001078880.1	Q4G0N4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NADK2	ENST00000381937.9 linkuse as main transcript	c.1104G>A	p.Pro368Pro	synonymous_variant	11/12	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

GnomAD3 exomes

AF:

0.00847

AC:

2097

AN:

247550

Hom.:

AF XY:

0.00866

AC XY:

1160

AN XY:

133924

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 SAS exome

AF:

0.00904

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

Gnomad4 AFR exome

AF:

0.00968

Gnomad4 AMR exome

AF:

0.00504

Gnomad4 ASJ exome

AF:

0.00783

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00971

Gnomad4 FIN exome

AF:

0.00431

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.00962

AC:

1460

AN:

151754

Hom.:

Cov.:

AF XY:

0.00942

AC XY:

698

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.00441

Gnomad4 ASJ

AF:

0.00751

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00895

Gnomad4 FIN

AF:

0.00399

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00952

Alfa

AF:

0.0110

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

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	NADK2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 07, 2016

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 28, 2019

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.4

DANN

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over