rs6891700

Variant names:

• chr5-36241541-C-T
• rs6891700
• NM_001085411.3:c.258G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-36241541-C-T
• chr5-36241541-C-A

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.258G>A​(p.Arg86Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,569,272 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (811 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (681 hom.)
• Consequence: NADK2 NM_001085411.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.414
• Publications: 2 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=-0.34).
• BP6: Variant 5-36241541-C-T is Benign according to our data. Variant chr5-36241541-C-T is described in ClinVar as Benign. ClinVar VariationId is 380097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.414 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 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.258G>A	p.Arg86Arg	synonymous	Exon 1 of 12	NP_001078880.1	Q4G0N4-1
	NADK2	NM_001287341.2		c.-190+555G>A		intron	N/A	NP_001274270.1	B7Z8V7
	NADK2	NM_153013.5		c.-190+555G>A		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.258G>A	p.Arg86Arg	synonymous	Exon 1 of 12	ENSP00000371362.4	Q4G0N4-1
	NADK2	ENST00000282512.7	TSL:1	c.-190+555G>A		intron	N/A	ENSP00000282512.3	Q4G0N4-3
	NADK2	ENST00000948923.1		c.258G>A	p.Arg86Arg	synonymous	Exon 1 of 13	ENSP00000618982.1

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8553 AN: 151956 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0412

GnomAD2 exomes AF: 0.0124 AC: 2276 AN: 184008 AF XY: 0.0106

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.00814

Gnomad ASJ exome AF: 0.00589

Gnomad EAS exome AF: 0.0000762

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000746

Gnomad OTH exome AF: 0.00614

GnomAD4 exome AF: 0.00641 AC: 9087 AN: 1417198 Hom.: 681 Cov.: 31 AF XY: 0.00612 AC XY: 4306 AN XY: 703838

African (AFR) AF: 0.199 AC: 6109 AN: 30644

American (AMR) AF: 0.00935 AC: 396 AN: 42356

Ashkenazi Jewish (ASJ) AF: 0.00751 AC: 189 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 36066

South Asian (SAS) AF: 0.0132 AC: 1095 AN: 82836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36850

Middle Eastern (MID) AF: 0.0106 AC: 58 AN: 5486

European-Non Finnish (NFE) AF: 0.000355 AC: 390 AN: 1098728

Other (OTH) AF: 0.0144 AC: 850 AN: 59056

GnomAD4 genome AF: 0.0565 AC: 8594 AN: 152074 Hom.: 811 Cov.: 32 AF XY: 0.0545 AC XY: 4055 AN XY: 74376

African (AFR) AF: 0.195 AC: 8082 AN: 41472

American (AMR) AF: 0.0181 AC: 277 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 67968

Other (OTH) AF: 0.0408 AC: 86 AN: 2108

Alfa AF: 0.0250 Hom.: 70

Bravo AF: 0.0636

Asia WGS AF: 0.0230 AC: 79 AN: 3478

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	-0.34
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		-0.41
PromoterAI		0.079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6891700; hg19: chr5-36241643;