NM_000904.6:c.-85-2169T>C

Variant names:

• chr6-3004299-T-C
• rs2756075
• NM_000904.6:c.-85-2169T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO2	NM_000904.6	MANE Select	c.-85-2169T>C		intron	N/A	NP_000895.2
	NQO2	NM_001290221.2		c.-242-196T>C		intron	N/A	NP_001277150.1
	NQO2	NM_001318940.2		c.-85-2169T>C		intron	N/A	NP_001305869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO2	ENST00000380455.11	TSL:1 MANE Select	c.-85-2169T>C		intron	N/A	ENSP00000369822.4
	NQO2	ENST00000338130.7	TSL:2	c.-242-196T>C		intron	N/A	ENSP00000337773.2
	NQO2	ENST00000380430.6	TSL:5	c.-85-2169T>C		intron	N/A	ENSP00000369795.1

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

African (AFR) AF: 0.796 AC: 12282 AN: 15438

American (AMR) AF: 0.595 AC: 580 AN: 974

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 2828 AN: 5110

East Asian (EAS) AF: 0.482 AC: 1735 AN: 3598

South Asian (SAS) AF: 0.656 AC: 10741 AN: 16364

European-Finnish (FIN) AF: 0.687 AC: 191 AN: 278

Middle Eastern (MID) AF: 0.590 AC: 955 AN: 1618

European-Non Finnish (NFE) AF: 0.644 AC: 487406 AN: 757146

Other (OTH) AF: 0.643 AC: 17431 AN: 27116

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

African (AFR) AF: 0.779 AC: 32018 AN: 41106

American (AMR) AF: 0.624 AC: 9506 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1978 AN: 3464

East Asian (EAS) AF: 0.491 AC: 2525 AN: 5142

South Asian (SAS) AF: 0.634 AC: 3036 AN: 4792

European-Finnish (FIN) AF: 0.662 AC: 6981 AN: 10540

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.641 AC: 43444 AN: 67812

Other (OTH) AF: 0.635 AC: 1334 AN: 2102

Alfa AF: 0.588 Hom.: 2615

Bravo AF: 0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.8
DANN	Benign	0.57
PhyloP100		0.17
PromoterAI		0.00070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2756075; hg19: chr6-3004533;