rs2071004

Positions:

• chr6-3000103-G-A

Variant summary

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

The NM_000904.6(NQO2):​c.-86+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,280 control chromosomes in the GnomAD database, including 3,716 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 0.22 (3707 hom., cov: 33)
  • Exomes 𝑓: 0.26 (9 hom.)
• Consequence: NQO2 NM_000904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO2	NM_000904.6	c.-86+18G>A		intron_variant		ENST00000380455.11	NP_000895.2
NQO2	NM_001318940.2	c.-350G>A		5_prime_UTR_variant	1/7		NP_001305869.1
NQO2	NM_001290221.2	c.-601+18G>A		intron_variant			NP_001277150.1
NQO2	NM_001290222.2	c.-86+18G>A		intron_variant			NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11	c.-86+18G>A		intron_variant		1	NM_000904.6	ENSP00000369822	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33027 AN: 151890 Hom.: 3707 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.255 AC: 70 AN: 274 Hom.: 9 Cov.: 0 AF XY: 0.258 AC XY: 49 AN XY: 190

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.217 AC: 33029 AN: 152006 Hom.: 3707 Cov.: 33 AF XY: 0.215 AC XY: 15987 AN XY: 74270

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.256

Alfa AF: 0.216 Hom.: 831

Bravo AF: 0.225

Asia WGS AF: 0.321 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.7
DANN	Benign	0.89
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.9

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: rs2071004; hg19: chr6-3000337;