rs79189380

Variant names:

• chr5-36197627-C-T
• rs79189380
• NM_001085411.3:c.1104G>A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0910

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]

ACMG classification

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 rank	MANE	Protein	UniProt
NADK2	NM_001085411.3	c.1104G>A	p.Pro368Pro	synonymous_variant	Exon 11 of 12	ENST00000381937.9	NP_001078880.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00962 AC: 1458 AN: 151636 Hom.: 11 Cov.: 32

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.: 11 AF XY: 0.00866 AC XY: 1160 AN XY: 133924

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.: 30 AF XY: 0.0120 AC XY: 8682 AN XY: 724950

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.: 11 Cov.: 32 AF XY: 0.00942 AC XY: 698 AN XY: 74126

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.: 5

Bravo AF: 0.00993

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0126

EpiControl AF: 0.0131

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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 -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
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

Other links and lift over

dbSNP: rs79189380; hg19: chr5-36197729;