Variant 5-36195346-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001085411.3(NADK2):c.1191-64T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,465,232 control chromosomes in the GnomAD database, including 212,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 16068 hom., cov: 32)

Exomes 𝑓: 0.53 ( 196240 hom. )

Consequence

NADK2
NM_001085411.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.625

Variant links:

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 links:

SKP2 (HGNC:10901): (S-phase kinase associated protein 2) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011]

SKP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-36195346-A-G is Benign according to our data. Variant chr5-36195346-A-G is described in ClinVar as [Benign]. Clinvar id is 1235193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NADK2	NM_001085411.3 linkuse as main transcript	c.1191-64T>C		intron_variant		ENST00000381937.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADK2	ENST00000381937.9 linkuse as main transcript	c.1191-64T>C		intron_variant		2	NM_001085411.3	P1	Q4G0N4-1

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63607

AN:

151926

Hom.:

16069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.0857

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.430

GnomAD4 exome

AF:

0.533

AC:

699310

AN:

1313188

Hom.:

196240

AF XY:

0.528

AC XY:

341588

AN XY:

646614

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.0885

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.542

Gnomad4 NFE exome

AF:

0.580

Gnomad4 OTH exome

AF:

0.485

GnomAD4 genome

AF:

0.418

AC:

63605

AN:

152044

Hom.:

16068

Cov.:

AF XY:

0.411

AC XY:

30544

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.427

Gnomad4 ASJ

AF:

0.567

Gnomad4 EAS

AF:

0.0861

Gnomad4 SAS

AF:

0.247

Gnomad4 FIN

AF:

0.542

Gnomad4 NFE

AF:

0.576

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.366

Hom.:

1135

Bravo

AF:

0.400

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.40

DANN

Benign

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over