rs10454863

Positions:

• chr5-36238185-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085411.3(NADK2):​c.300+3314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,954 control chromosomes in the GnomAD database, including 19,206 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19206 hom., cov: 32)
• Consequence: NADK2 NM_001085411.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NADK2	NM_001085411.3	c.300+3314C>T		intron_variant		ENST00000381937.9	NP_001078880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NADK2	ENST00000381937.9	c.300+3314C>T		intron_variant		2	NM_001085411.3	ENSP00000371362.4

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74144 AN: 151836 Hom.: 19192 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.467

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74191 AN: 151954 Hom.: 19206 Cov.: 32 AF XY: 0.478 AC XY: 35509 AN XY: 74294

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.463

Alfa AF: 0.552 Hom.: 37786

Bravo AF: 0.478

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.58

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: rs10454863; hg19: chr5-36238287;