Variant chr6-3010064-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000904.6(NQO2):c.47A>G(p.Lys16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,613,998 control chromosomes in the GnomAD database, including 936 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.037 ( 119 hom., cov: 32)

Exomes 𝑓: 0.032 ( 817 hom. )

Consequence

NQO2
NM_000904.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.753

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027751625).

BP6

Variant 6-3010064-A-G is Benign according to our data. Variant chr6-3010064-A-G is described in ClinVar as [Benign]. Clinvar id is 2445265.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NQO2	NM_000904.6 linkuse as main transcript	c.47A>G	p.Lys16Arg	missense_variant	3/7	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2 linkuse as main transcript	c.47A>G	p.Lys16Arg	missense_variant	6/10		NP_001277150.1
NQO2	NM_001318940.2 linkuse as main transcript	c.47A>G	p.Lys16Arg	missense_variant	3/7		NP_001305869.1
NQO2	NM_001290222.2 linkuse as main transcript	c.47A>G	p.Lys16Arg	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.47A>G	p.Lys16Arg	missense_variant	3/7	1	NM_000904.6	ENSP00000369822	P1

Frequencies

GnomAD3 genomes

AF:

0.0373

AC:

5672

AN:

152094

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0552

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0366

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.0248

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0426

GnomAD3 exomes

AF:

0.0247

AC:

6219

AN:

251426

Hom.:

103

AF XY:

0.0232

AC XY:

3157

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0515

Gnomad AMR exome

AF:

0.0171

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.00340

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0259

GnomAD4 exome

AF:

0.0318

AC:

46491

AN:

1461788

Hom.:

817

Cov.:

AF XY:

0.0309

AC XY:

22465

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0536

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0297

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.00403

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0352

Gnomad4 OTH exome

AF:

0.0336

GnomAD4 genome

AF:

0.0373

AC:

5674

AN:

152210

Hom.:

119

Cov.:

AF XY:

0.0341

AC XY:

2541

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0551

Gnomad4 AMR

AF:

0.0365

Gnomad4 ASJ

AF:

0.0279

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0248

Gnomad4 NFE

AF:

0.0344

Gnomad4 OTH

AF:

0.0422

Alfa

AF:

0.0319

Hom.:

193

Bravo

AF:

0.0381

TwinsUK

AF:

0.0267

AC:

ALSPAC

AF:

0.0363

AC:

140

ESP6500AA

AF:

0.0538

AC:

237

ESP6500EA

AF:

0.0377

AC:

324

ExAC

AF:

0.0251

AC:

3044

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.0321

EpiControl

AF:

0.0332

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ovarian cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.11

DANN

Benign

0.81

DEOGEN2

Benign

0.079

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

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.67

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

MetaRNN

Benign

0.0028

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

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.25

.;.;.;N;.;N;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.95

N;N;N;N;N;N;N;N

REVEL

Benign

0.030

Sift

Benign

0.97

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

Sift4G

Benign

0.67

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

Polyphen

0.0

.;.;.;B;.;B;.;B

Vest4

0.028, 0.12, 0.12

MPC

0.067

ClinPred

0.00030

GERP RS

-7.5

Varity_R

0.072

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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