chr6-3012621-G-T
Position:
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
NM_000904.6 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 6.00
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]
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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 |
---|---|---|---|---|---|---|---|---|
NQO2 | NM_000904.6 | c.250G>T | p.Asp84Tyr | missense_variant | 4/7 | ENST00000380455.11 | NP_000895.2 | |
NQO2 | NM_001290221.2 | c.250G>T | p.Asp84Tyr | missense_variant | 7/10 | NP_001277150.1 | ||
NQO2 | NM_001318940.2 | c.250G>T | p.Asp84Tyr | missense_variant | 4/7 | NP_001305869.1 | ||
NQO2 | NM_001290222.2 | c.250G>T | p.Asp84Tyr | missense_variant | 4/6 | NP_001277151.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NQO2 | ENST00000380455.11 | c.250G>T | p.Asp84Tyr | missense_variant | 4/7 | 1 | NM_000904.6 | ENSP00000369822 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 31
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 submitter | clinical testing | Ambry Genetics | Mar 30, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;.;.;.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;.;H;.;H;.;H
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;D;.;D
Vest4
0.70, 0.75, 0.70, 0.81
MutPred
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
MPC
0.50
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.