NADK2 p.Arg70Arg

Variant names:

• chr5-36241588-C-C
• NM_001085411.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr5-36241589--
• chr5-36241589-C-A
• chr5-36241589-C-G
• chr5-36241589-C-T
• chr5-36241591-G-T
• chr5-36241589-CCG-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001085411.3(NADK2):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NADK2 NM_001085411.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085411.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADK2	NM_001085411.3	MANE Select	c.		exon_region	Exon 1 of 12	NP_001078880.1	Q4G0N4-1
	NADK2	NM_001287341.2		c.		intron	N/A	NP_001274270.1	B7Z8V7
	NADK2	NM_153013.5		c.		intron	N/A	NP_694558.1	Q4G0N4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADK2	ENST00000381937.9	TSL:2 MANE Select	c.		exon_region	Exon 1 of 12	ENSP00000371362.4	Q4G0N4-1
	NADK2	ENST00000282512.7	TSL:1	c.		intron	N/A	ENSP00000282512.3	Q4G0N4-3
	NADK2	ENST00000948923.1		c.		exon_region	Exon 1 of 13	ENSP00000618982.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-36241690;