Genetic Variant NM_000904.6:c.7+14A>G (chr6-3006573-A-G) – 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.7+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,588,476 control chromosomes in the GnomAD database, including 34,947 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 0.16 ( 2436 hom., cov: 31)

Exomes 𝑓: 0.21 ( 32511 hom. )

Consequence

NQO2
NM_000904.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.338

Publications

22 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NQO2	NM_000904.6 link	c.7+14A>G	intron_variant	Intron 2 of 6	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2 link	c.7+14A>G	intron_variant	Intron 5 of 9		NP_001277150.1
NQO2	NM_001318940.2 link	c.7+14A>G	intron_variant	Intron 2 of 6		NP_001305869.1
NQO2	NM_001290222.2 link	c.7+14A>G	intron_variant	Intron 2 of 5		NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11 link	c.7+14A>G		intron_variant	Intron 2 of 6	1	NM_000904.6	ENSP00000369822.4		P16083

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24340

AN:

151554

Hom.:

2435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.187

AC:

39489

AN:

210714

AF XY:

0.187

show subpopulations

Gnomad AFR exome

AF:

0.0573

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.206

AC:

296168

AN:

1436804

Hom.:

32511

Cov.:

AF XY:

0.203

AC XY:

145082

AN XY:

713480

show subpopulations

African (AFR)

AF:

0.0526

AC:

1691

AN:

32152

American (AMR)

AF:

0.193

AC:

7684

AN:

39878

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

3510

AN:

25574

East Asian (EAS)

AF:

0.100

AC:

3888

AN:

38698

South Asian (SAS)

AF:

0.114

AC:

9314

AN:

81364

European-Finnish (FIN)

AF:

0.214

AC:

11242

AN:

52490

Middle Eastern (MID)

AF:

0.111

AC:

632

AN:

5688

European-Non Finnish (NFE)

AF:

0.224

AC:

247238

AN:

1101576

Other (OTH)

AF:

0.185

AC:

10969

AN:

59384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

11500

23000

34499

45999

57499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8420

16840

25260

33680

42100

<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:

0.161

AC:

24345

AN:

151672

Hom.:

2436

Cov.:

AF XY:

0.161

AC XY:

11953

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.0551

AC:

2281

AN:

41366

American (AMR)

AF:

0.179

AC:

2722

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3468

East Asian (EAS)

AF:

0.123

AC:

634

AN:

5150

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4812

European-Finnish (FIN)

AF:

0.221

AC:

2312

AN:

10446

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14802

AN:

67888

Other (OTH)

AF:

0.153

AC:

322

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

998

1997

2995

3994

4992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.193

Hom.:

5381

Bravo

AF:

0.155

Asia WGS

AF:

0.118

AC:

409

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.040

(source)

DANN

Benign

0.32

PhyloP100

-0.34

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over