6-3009710-A-G

Variant names:

• chr6-3009710-A-G
• rs2518581
• NM_000904.6:c.8-315A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000904.6(NQO2):​c.8-315A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,146 control chromosomes in the GnomAD database, including 46,458 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 0.78 (46458 hom., cov: 31)
• Consequence: NQO2 NM_000904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 11 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 = 0.87 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO2	NM_000904.6	MANE Select	c.8-315A>G		intron	N/A	NP_000895.2	P16083
	NQO2	NM_001290221.2		c.8-315A>G		intron	N/A	NP_001277150.1	P16083
	NQO2	NM_001318940.2		c.8-315A>G		intron	N/A	NP_001305869.1	P16083

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO2	ENST00000380455.11	TSL:1 MANE Select	c.8-315A>G		intron	N/A	ENSP00000369822.4	P16083
	NQO2	ENST00000952452.1		c.8-270A>G		intron	N/A	ENSP00000622511.1
	NQO2	ENST00000338130.7	TSL:2	c.8-315A>G		intron	N/A	ENSP00000337773.2	P16083

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118354 AN: 152028 Hom.: 46403 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.742

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.779 AC: 118465 AN: 152146 Hom.: 46458 Cov.: 31 AF XY: 0.776 AC XY: 57719 AN XY: 74380

African (AFR) AF: 0.878 AC: 36435 AN: 41500

American (AMR) AF: 0.741 AC: 11332 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2315 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3371 AN: 5172

South Asian (SAS) AF: 0.705 AC: 3399 AN: 4820

European-Finnish (FIN) AF: 0.764 AC: 8078 AN: 10576

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51064 AN: 68002

Other (OTH) AF: 0.743 AC: 1570 AN: 2112

Alfa AF: 0.748 Hom.: 2861

Bravo AF: 0.780

Asia WGS AF: 0.680 AC: 2364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-1.9
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: rs2518581; hg19: chr6-3009944;