chr6-3002004-T-C

Position:

• chr6-3002004-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.-86+1919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 153,300 control chromosomes in the GnomAD database, including 46,878 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 (46501 hom., cov: 31)
  • Exomes 𝑓: 0.80 (377 hom.)
• Consequence: NQO2 NM_000904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NQO2	NM_000904.6	c.-86+1919T>C		intron_variant		ENST00000380455.11
NQO2	NM_001290221.2	c.-600-46T>C		intron_variant
NQO2	NM_001290222.2	c.-86+1919T>C		intron_variant
NQO2	NM_001318940.2	c.-86+1637T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NQO2	ENST00000380455.11	c.-86+1919T>C		intron_variant		1	NM_000904.6	P1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118645 AN: 151994 Hom.: 46449 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.798 AC: 948 AN: 1188 Hom.: 377 Cov.: 0 AF XY: 0.813 AC XY: 520 AN XY: 640

Gnomad4 AFR exome AF: 0.714

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.889

GnomAD4 genome AF: 0.781 AC: 118757 AN: 152112 Hom.: 46501 Cov.: 31 AF XY: 0.784 AC XY: 58269 AN XY: 74358

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.751

Alfa AF: 0.757 Hom.: 69323

Bravo AF: 0.774

Asia WGS AF: 0.692 AC: 2405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.53

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: rs4149352; hg19: chr6-3002238;