dbSNP rs2071002: NQO2:c.-102A>C (chr6-3000069-A-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.-102A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,384 control chromosomes in the GnomAD database, including 8,051 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 0.32 ( 8033 hom., cov: 33)

Exomes 𝑓: 0.29 ( 18 hom. )

Consequence

NQO2
NM_000904.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.396

Publications

39 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:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 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.-102A>C	5_prime_UTR	Exon 1 of 7	NP_000895.2	P16083
NQO2	NM_001290221.2		c.-617A>C	5_prime_UTR	Exon 1 of 10	NP_001277150.1	P16083
NQO2	NM_001318940.2		c.-384A>C	5_prime_UTR	Exon 1 of 7	NP_001305869.1	P16083

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NQO2	ENST00000380455.11	TSL:1 MANE Select	c.-102A>C	5_prime_UTR	Exon 1 of 7	ENSP00000369822.4	P16083
NQO2	ENST00000952452.1		c.-102A>C	5_prime_UTR	Exon 1 of 7	ENSP00000622511.1
NQO2	ENST00000338130.7	TSL:2	c.-617A>C	5_prime_UTR	Exon 1 of 10	ENSP00000337773.2	P16083

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

49002

AN:

151958

Hom.:

8011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.292

AC:

AN:

308

Hom.:

Cov.:

AF XY:

0.277

AC XY:

AN XY:

238

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.280

AC:

AN:

268

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.323

AC:

49077

AN:

152076

Hom.:

8033

Cov.:

AF XY:

0.321

AC XY:

23867

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.372

AC:

15429

AN:

41506

American (AMR)

AF:

0.329

AC:

5033

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

722

AN:

3468

East Asian (EAS)

AF:

0.347

AC:

1784

AN:

5138

South Asian (SAS)

AF:

0.281

AC:

1355

AN:

4824

European-Finnish (FIN)

AF:

0.295

AC:

3123

AN:

10588

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20744

AN:

67942

Other (OTH)

AF:

0.305

AC:

644

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1774

3549

5323

7098

8872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.291

Hom.:

9839

Bravo

AF:

0.329

Asia WGS

AF:

0.292

AC:

1013

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

(source)

DANN

Benign

0.64

PhyloP100

-0.40

PromoterAI

0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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