6-3019637-C-G

Variant names:

• chr6-3019637-C-G
• NM_000904.6:c.678C>G
• NQO2 p.His226Gln

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000904.6(NQO2):​c.678C>G​(p.His226Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NQO2 NM_000904.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 0 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]

HTATSF1P2 (HGNC:38586): (HIV-1 Tat specific factor 1 pseudogene 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03933379).

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.678C>G	p.His226Gln	missense	Exon 7 of 7	NP_000895.2	P16083
	NQO2	NM_001290221.2		c.678C>G	p.His226Gln	missense	Exon 10 of 10	NP_001277150.1	P16083
	NQO2	NM_001318940.2		c.678C>G	p.His226Gln	missense	Exon 7 of 7	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.678C>G	p.His226Gln	missense	Exon 7 of 7	ENSP00000369822.4	P16083
	NQO2	ENST00000952452.1		c.723C>G	p.His241Gln	missense	Exon 7 of 7	ENSP00000622511.1
	NQO2	ENST00000338130.7	TSL:2	c.678C>G	p.His226Gln	missense	Exon 10 of 10	ENSP00000337773.2	P16083

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.016
DANN	Benign	0.53
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.98
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.012
Sift	Benign	0.29	T
Sift4G	Benign	0.21	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.73
Mutation Taster		=84/16	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-3019871;