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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NQO2	NM_000904.6 link	c.-102A>C	5_prime_UTR_variant	Exon 1 of 7	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2 link	c.-617A>C	5_prime_UTR_variant	Exon 1 of 10		NP_001277150.1
NQO2	NM_001318940.2 link	c.-384A>C	5_prime_UTR_variant	Exon 1 of 7		NP_001305869.1
NQO2	NM_001290222.2 link	c.-102A>C	5_prime_UTR_variant	Exon 1 of 6		NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11 link	c.-102A>C		5_prime_UTR_variant	Exon 1 of 7	1	NM_000904.6	ENSP00000369822.4		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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over