dbSNP rs2071004: NQO2:c.-86+18G>A (chr6-3000103-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000904.6(NQO2):c.-86+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,280 control chromosomes in the GnomAD database, including 3,716 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 0.22 ( 3707 hom., cov: 33)

Exomes 𝑓: 0.26 ( 9 hom. )

Consequence

NQO2
NM_000904.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.129

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NQO2	NM_000904.6 link	c.-86+18G>A	intron_variant	Intron 1 of 6	ENST00000380455.11	NP_000895.2
NQO2	NM_001318940.2 link	c.-350G>A	5_prime_UTR_variant	Exon 1 of 7		NP_001305869.1
NQO2	NM_001290221.2 link	c.-601+18G>A	intron_variant	Intron 1 of 9		NP_001277150.1
NQO2	NM_001290222.2 link	c.-86+18G>A	intron_variant	Intron 1 of 5		NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11 link	c.-86+18G>A		intron_variant	Intron 1 of 6	1	NM_000904.6	ENSP00000369822.4		P16083

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33027

AN:

151890

Hom.:

3707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.257

GnomAD4 exome

AF:

0.255

AC:

AN:

274

Hom.:

Cov.:

AF XY:

0.258

AC XY:

AN XY:

190

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.245

AC:

AN:

216

Other (OTH)

AF:

0.444

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.217

AC:

33029

AN:

152006

Hom.:

3707

Cov.:

AF XY:

0.215

AC XY:

15987

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.172

AC:

7146

AN:

41500

American (AMR)

AF:

0.256

AC:

3913

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1037

AN:

3464

East Asian (EAS)

AF:

0.378

AC:

1933

AN:

5120

South Asian (SAS)

AF:

0.260

AC:

1251

AN:

4820

European-Finnish (FIN)

AF:

0.150

AC:

1584

AN:

10584

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.226

AC:

15337

AN:

67924

Other (OTH)

AF:

0.256

AC:

541

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1345

2689

4034

5378

6723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

831

Bravo

AF:

0.225

Asia WGS

AF:

0.321

AC:

1118

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.7

(source)

DANN

Benign

0.89

PhyloP100

-0.13

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over