chr6-3012621-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000904.6(NQO2):​c.250G>T​(p.Asp84Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

NQO2
NM_000904.6 missense

Scores

10
5
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NQO2NM_000904.6 linkuse as main transcriptc.250G>T p.Asp84Tyr missense_variant 4/7 ENST00000380455.11 NP_000895.2
NQO2NM_001290221.2 linkuse as main transcriptc.250G>T p.Asp84Tyr missense_variant 7/10 NP_001277150.1
NQO2NM_001318940.2 linkuse as main transcriptc.250G>T p.Asp84Tyr missense_variant 4/7 NP_001305869.1
NQO2NM_001290222.2 linkuse as main transcriptc.250G>T p.Asp84Tyr missense_variant 4/6 NP_001277151.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NQO2ENST00000380455.11 linkuse as main transcriptc.250G>T p.Asp84Tyr missense_variant 4/71 NM_000904.6 ENSP00000369822 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 30, 2024The c.250G>T (p.D84Y) alteration is located in exon 4 (coding exon 3) of the NQO2 gene. This alteration results from a G to T substitution at nucleotide position 250, causing the aspartic acid (D) at amino acid position 84 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.40
.;.;T;.;T;.;T
Eigen
Pathogenic
0.95
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
.;D;.;.;.;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.98
D;D;D;D;D;D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Pathogenic
4.5
.;.;H;.;H;.;H
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-8.7
D;D;D;D;D;D;D
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;D;.;D
Vest4
0.70, 0.75, 0.70, 0.81
MutPred
0.81
Loss of disorder (P = 0.0123);Loss of disorder (P = 0.0123);Loss of disorder (P = 0.0123);Loss of disorder (P = 0.0123);Loss of disorder (P = 0.0123);Loss of disorder (P = 0.0123);Loss of disorder (P = 0.0123);
MVP
0.56
MPC
0.50
ClinPred
1.0
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.98
gMVP
0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-3012855; API