Genetic Variant NQO2:c.-85-2169T>G (chr6-3004299-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000904.6(NQO2):c.-85-2169T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 981,472 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000023 ( 0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.-85-2169T>G	intron	N/A	NP_000895.2
NQO2	NM_001290221.2		c.-242-196T>G	intron	N/A	NP_001277150.1
NQO2	NM_001318940.2		c.-85-2169T>G	intron	N/A	NP_001305869.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NQO2	ENST00000380455.11	TSL:1 MANE Select	c.-85-2169T>G	intron	N/A	ENSP00000369822.4
NQO2	ENST00000338130.7	TSL:2	c.-242-196T>G	intron	N/A	ENSP00000337773.2
NQO2	ENST00000380430.6	TSL:5	c.-85-2169T>G	intron	N/A	ENSP00000369795.1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000229

AC:

AN:

829940

Hom.:

Cov.:

AF XY:

0.0000313

AC XY:

AN XY:

383414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15520

American (AMR)

AF:

0.00

AC:

AN:

978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5134

East Asian (EAS)

AF:

0.00

AC:

AN:

3610

South Asian (SAS)

AF:

0.00

AC:

AN:

16408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.0000250

AC:

AN:

759204

Other (OTH)

AF:

0.00

AC:

AN:

27188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000660

AC:

AN:

151532

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41070

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67910

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

2615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.4

(source)

DANN

Benign

0.53

PhyloP100

0.17

PromoterAI

0.011

Neutral

(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