6-3009710-A-G

Position:

• chr6-3009710-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.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

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 = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO2	NM_000904.6	c.8-315A>G		intron_variant		ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2	c.8-315A>G		intron_variant			NP_001277150.1
NQO2	NM_001290222.2	c.8-315A>G		intron_variant			NP_001277151.1
NQO2	NM_001318940.2	c.8-315A>G		intron_variant			NP_001305869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11	c.8-315A>G		intron_variant		1	NM_000904.6	ENSP00000369822	P1

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

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.743

Alfa AF: 0.737 Hom.: 2568

Bravo AF: 0.780

Asia WGS AF: 0.680 AC: 2364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.36

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: rs2518581; hg19: chr6-3009944;