Genetic Variant NQO2:c.-85-2169T>C (chr6-3004299-T-C) – 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.-85-2169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 979,026 control chromosomes in the GnomAD database, including 207,330 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 0.67 ( 34547 hom., cov: 28)

Exomes 𝑓: 0.65 ( 172783 hom. )

Consequence

NQO2
NM_000904.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170

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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 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	UniProt
NQO2	NM_000904.6	MANE Select	c.-85-2169T>C	intron	N/A	NP_000895.2	P16083
NQO2	NM_001290221.2		c.-242-196T>C	intron	N/A	NP_001277150.1	P16083
NQO2	NM_001318940.2		c.-85-2169T>C	intron	N/A	NP_001305869.1	P16083

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NQO2	ENST00000380455.11	TSL:1 MANE Select	c.-85-2169T>C	intron	N/A	ENSP00000369822.4	P16083
NQO2	ENST00000892240.1		c.-438T>C	5_prime_UTR	Exon 2 of 8	ENSP00000562299.1
NQO2	ENST00000929216.1		c.-2254T>C	5_prime_UTR	Exon 2 of 7	ENSP00000599275.1

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

101473

AN:

151266

Hom.:

34497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.632

GnomAD4 exome

AF:

0.645

AC:

534149

AN:

827642

Hom.:

172783

Cov.:

AF XY:

0.646

AC XY:

247064

AN XY:

382418

show subpopulations

African (AFR)

AF:

0.796

AC:

12282

AN:

15438

American (AMR)

AF:

0.595

AC:

580

AN:

974

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

2828

AN:

5110

East Asian (EAS)

AF:

0.482

AC:

1735

AN:

3598

South Asian (SAS)

AF:

0.656

AC:

10741

AN:

16364

European-Finnish (FIN)

AF:

0.687

AC:

191

AN:

278

Middle Eastern (MID)

AF:

0.590

AC:

955

AN:

1618

European-Non Finnish (NFE)

AF:

0.644

AC:

487406

AN:

757146

Other (OTH)

AF:

0.643

AC:

17431

AN:

27116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

8477

16954

25431

33908

42385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17546

35092

52638

70184

87730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.671

AC:

101576

AN:

151384

Hom.:

34547

Cov.:

AF XY:

0.672

AC XY:

49688

AN XY:

73960

show subpopulations

African (AFR)

AF:

0.779

AC:

32018

AN:

41106

American (AMR)

AF:

0.624

AC:

9506

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1978

AN:

3464

East Asian (EAS)

AF:

0.491

AC:

2525

AN:

5142

South Asian (SAS)

AF:

0.634

AC:

3036

AN:

4792

European-Finnish (FIN)

AF:

0.662

AC:

6981

AN:

10540

Middle Eastern (MID)

AF:

0.469

AC:

137

AN:

292

European-Non Finnish (NFE)

AF:

0.641

AC:

43444

AN:

67812

Other (OTH)

AF:

0.635

AC:

1334

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

1518

3036

4553

6071

7589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.588

Hom.:

2615

Bravo

AF:

0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.8

(source)

DANN

Benign

0.57

PhyloP100

0.17

PromoterAI

0.00070

Neutral

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over