rs189482969

Variant names:

• chr5-36241589-C-A
• rs189482969
• NM_001085411.3:c.210G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-36241589-C-A
• chr5-36241589-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001085411.3(NADK2):​c.210G>T​(p.Arg70Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,525,408 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R70R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.025 (158 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (123 hom.)
• Consequence: NADK2 NM_001085411.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 5-36241589-C-A is Benign according to our data. Variant chr5-36241589-C-A is described in ClinVar as Benign. ClinVar VariationId is 380096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

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.210G>T	p.Arg70Arg	synonymous	Exon 1 of 12	NP_001078880.1	Q4G0N4-1
	NADK2	NM_001287341.2		c.-190+507G>T		intron	N/A	NP_001274270.1	B7Z8V7
	NADK2	NM_153013.5		c.-190+507G>T		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.210G>T	p.Arg70Arg	synonymous	Exon 1 of 12	ENSP00000371362.4	Q4G0N4-1
	NADK2	ENST00000282512.7	TSL:1	c.-190+507G>T		intron	N/A	ENSP00000282512.3	Q4G0N4-3
	NADK2	ENST00000948923.1		c.210G>T	p.Arg70Arg	synonymous	Exon 1 of 13	ENSP00000618982.1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3730 AN: 151620 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00775

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00315 AC: 420 AN: 133150 AF XY: 0.00267

Gnomad AFR exome AF: 0.0852

Gnomad AMR exome AF: 0.00288

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000143

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000225

Gnomad OTH exome AF: 0.00174

GnomAD4 exome AF: 0.00234 AC: 3209 AN: 1373672 Hom.: 123 Cov.: 31 AF XY: 0.00203 AC XY: 1385 AN XY: 680994

African (AFR) AF: 0.0923 AC: 2613 AN: 28314

American (AMR) AF: 0.00395 AC: 141 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24252

East Asian (EAS) AF: 0.00 AC: 0 AN: 31064

South Asian (SAS) AF: 0.000178 AC: 14 AN: 78764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34892

Middle Eastern (MID) AF: 0.00306 AC: 15 AN: 4898

European-Non Finnish (NFE) AF: 0.000115 AC: 124 AN: 1078700

Other (OTH) AF: 0.00529 AC: 302 AN: 57054

GnomAD4 genome AF: 0.0246 AC: 3739 AN: 151736 Hom.: 158 Cov.: 32 AF XY: 0.0236 AC XY: 1752 AN XY: 74168

African (AFR) AF: 0.0858 AC: 3559 AN: 41502

American (AMR) AF: 0.00774 AC: 118 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10452

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67802

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.00407 Hom.: 4

Bravo AF: 0.0280

Asia WGS AF: 0.00405 AC: 14 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Progressive encephalopathy with leukodystrophy due to DECR deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		1.6
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs189482969; hg19: chr5-36241691;