6-3004299-T-C

Position:

• chr6-3004299-T-C

Variant summary

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

The NM_000904.6(NQO2):​c.-85-2169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 979,026 control chromosomes in the GnomAD database, including 207,330 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 0.67 (34547 hom., cov: 28)
  • Exomes 𝑓: 0.65 (172783 hom.)
• Consequence: NQO2 NM_000904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO2	NM_000904.6	c.-85-2169T>C		intron_variant		ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2	c.-242-196T>C		intron_variant			NP_001277150.1
NQO2	NM_001290222.2	c.-85-2169T>C		intron_variant			NP_001277151.1
NQO2	NM_001318940.2	c.-85-2169T>C		intron_variant			NP_001305869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11	c.-85-2169T>C		intron_variant		1	NM_000904.6	ENSP00000369822	P1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101473 AN: 151266 Hom.: 34497 Cov.: 28

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.645 AC: 534149 AN: 827642 Hom.: 172783 Cov.: 18 AF XY: 0.646 AC XY: 247064 AN XY: 382418

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.671 AC: 101576 AN: 151384 Hom.: 34547 Cov.: 28 AF XY: 0.672 AC XY: 49688 AN XY: 73960

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.635

Alfa AF: 0.588 Hom.: 2615

Bravo AF: 0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.8
DANN	Benign	0.57

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: rs2756075; hg19: chr6-3004533;