Genetic Variant NQO2:c.-86+1919T>C (chr6-3002004-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.-86+1919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 153,300 control chromosomes in the GnomAD database, including 46,878 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 0.78 ( 46501 hom., cov: 31)

Exomes 𝑓: 0.80 ( 377 hom. )

Consequence

NQO2
NM_000904.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

12 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NQO2	NM_000904.6 link	c.-86+1919T>C	intron_variant	Intron 1 of 6	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2 link	c.-600-46T>C	intron_variant	Intron 1 of 9		NP_001277150.1
NQO2	NM_001318940.2 link	c.-86+1637T>C	intron_variant	Intron 1 of 6		NP_001305869.1
NQO2	NM_001290222.2 link	c.-86+1919T>C	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+1919T>C		intron_variant	Intron 1 of 6	1	NM_000904.6	ENSP00000369822.4

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118645

AN:

151994

Hom.:

46449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.825

Gnomad AMI

AF:

0.838

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.767

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.798

AC:

948

AN:

1188

Hom.:

377

Cov.:

AF XY:

0.813

AC XY:

520

AN XY:

640

show subpopulations

African (AFR)

AF:

0.714

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.650

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.803

AC:

886

AN:

1104

Other (OTH)

AF:

0.889

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.781

AC:

118757

AN:

152112

Hom.:

46501

Cov.:

AF XY:

0.784

AC XY:

58269

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.825

AC:

34238

AN:

41482

American (AMR)

AF:

0.745

AC:

11387

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

2307

AN:

3472

East Asian (EAS)

AF:

0.668

AC:

3448

AN:

5164

South Asian (SAS)

AF:

0.729

AC:

3515

AN:

4820

European-Finnish (FIN)

AF:

0.866

AC:

9173

AN:

10598

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.767

AC:

52153

AN:

67972

Other (OTH)

AF:

0.751

AC:

1584

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1364

2728

4093

5457

6821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.762

Hom.:

166110

Bravo

AF:

0.774

Asia WGS

AF:

0.692

AC:

2405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.6

(source)

DANN

Benign

0.53

PhyloP100

-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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over