rs2071002

Positions:

• chr6-3000069-A-C
• chr6-3000069-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO2	NM_000904.6	c.-102A>C		5_prime_UTR_variant	1/7	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2	c.-617A>C		5_prime_UTR_variant	1/10		NP_001277150.1
NQO2	NM_001290222.2	c.-102A>C		5_prime_UTR_variant	1/6		NP_001277151.1
NQO2	NM_001318940.2	c.-384A>C		5_prime_UTR_variant	1/7		NP_001305869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11	c.-102A>C		5_prime_UTR_variant	1/7	1	NM_000904.6	ENSP00000369822	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 49002 AN: 151958 Hom.: 8011 Cov.: 33

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: 90 AN: 308 Hom.: 18 Cov.: 0 AF XY: 0.277 AC XY: 66 AN XY: 238

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.323 AC: 49077 AN: 152076 Hom.: 8033 Cov.: 33 AF XY: 0.321 AC XY: 23867 AN XY: 74340

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.305

Alfa AF: 0.284 Hom.: 7326

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
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2071002; hg19: chr6-3000303;