Variant chr6-3010075-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000904.6(NQO2):c.58G>A(p.Gly20Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

NQO2
NM_000904.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Variant links:

Genes affected

NQO2 (HGNC:7856): (N-ribosyldihydronicotinamide:quinone dehydrogenase 2) This gene encodes a member of the thioredoxin family of enzymes. It is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone substrates and uses dihydronicotinamide riboside as a reducing coenzyme. Mutations in this gene have been associated with neurodegenerative diseases and several cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

NQO2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NQO2	NM_000904.6 linkuse as main transcript	c.58G>A	p.Gly20Arg	missense_variant	3/7	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2 linkuse as main transcript	c.58G>A	p.Gly20Arg	missense_variant	6/10		NP_001277150.1
NQO2	NM_001318940.2 linkuse as main transcript	c.58G>A	p.Gly20Arg	missense_variant	3/7		NP_001305869.1
NQO2	NM_001290222.2 linkuse as main transcript	c.58G>A	p.Gly20Arg	missense_variant	3/6		NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11 linkuse as main transcript	c.58G>A	p.Gly20Arg	missense_variant	3/7	1	NM_000904.6	ENSP00000369822	P1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251450

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000118

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.58G>A (p.G20R) alteration is located in exon 3 (coding exon 2) of the NQO2 gene. This alteration results from a G to A substitution at nucleotide position 58, causing the glycine (G) at amino acid position 20 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.21

.;.;.;T;.;T;.;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.080

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.99

D;.;D;.;.;.;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;.;.;L;.;L;.;L

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.3

D;D;D;D;D;D;D;D

REVEL

Benign

0.25

Sift

Benign

0.047

D;T;T;T;T;T;T;T

Sift4G

Benign

0.099

T;T;T;T;T;T;T;T

Polyphen

0.77

.;.;.;P;.;P;.;P

Vest4

0.65, 0.63, 0.64

MutPred

0.62

Loss of ubiquitination at K23 (P = 0.0461);Loss of ubiquitination at K23 (P = 0.0461);Loss of ubiquitination at K23 (P = 0.0461);Loss of ubiquitination at K23 (P = 0.0461);Loss of ubiquitination at K23 (P = 0.0461);Loss of ubiquitination at K23 (P = 0.0461);Loss of ubiquitination at K23 (P = 0.0461);Loss of ubiquitination at K23 (P = 0.0461);

MVP

0.26

MPC

0.49

ClinPred

0.28

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.88

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 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