rs2070999

Positions:

• chr6-2999495-A-G
• chr6-2999495-A-T

Variant summary

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

The ENST00000380472.7(NQO2):​c.-86+5442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,992 control chromosomes in the GnomAD database, including 37,774 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 0.69 (37774 hom., cov: 31)
• Consequence: NQO2 ENST00000380472.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

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]

NQO2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO2-AS1	NR_186364.1	n.181T>C		non_coding_transcript_exon_variant	1/2
NQO2-AS1	NR_186365.1	n.181T>C		non_coding_transcript_exon_variant	1/3
NQO2-AS1	NR_186366.1	n.181T>C		non_coding_transcript_exon_variant	1/2
NQO2-AS1	NR_186367.1	n.181T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380472.7	c.-86+5442A>G		intron_variant		5		ENSP00000369839.3
NQO2	ENST00000426637.5	c.-86+5442A>G		intron_variant		5		ENSP00000406951.1
NQO2-AS1	ENST00000660868.1	n.110T>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105149 AN: 151874 Hom.: 37722 Cov.: 31

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.692 AC: 105254 AN: 151992 Hom.: 37774 Cov.: 31 AF XY: 0.690 AC XY: 51262 AN XY: 74272

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.691

Alfa AF: 0.619 Hom.: 46375

Bravo AF: 0.712

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2070999; hg19: chr6-2999729; COSMIC: COSV57643748;