Genetic Variant 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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000904.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NQO2	NM_000904.6	MANE Select	c.-86+18G>A	intron	N/A	NP_000895.2
NQO2	NM_001318940.2		c.-350G>A	5_prime_UTR	Exon 1 of 7	NP_001305869.1
NQO2	NM_001290221.2		c.-601+18G>A	intron	N/A	NP_001277150.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NQO2	ENST00000380455.11	TSL:1 MANE Select	c.-86+18G>A	intron	N/A	ENSP00000369822.4
NQO2	ENST00000338130.7	TSL:2	c.-601+18G>A	intron	N/A	ENSP00000337773.2
NQO2	ENST00000380441.5	TSL:5	c.-243+18G>A	intron	N/A	ENSP00000369806.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over