Variant 6-3012539-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000904.6(NQO2):c.173-5G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,613,826 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 20 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 37 hom. )

Consequence

NQO2
NM_000904.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001215

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.497

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]

NQO2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-3012539-G-A is Benign according to our data. Variant chr6-3012539-G-A is described in ClinVar as [Benign]. Clinvar id is 778884.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0047 (716/152196) while in subpopulation AMR AF= 0.0366 (559/15276). AF 95% confidence interval is 0.0341. There are 20 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NQO2	NM_000904.6 linkuse as main transcript	c.173-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2 linkuse as main transcript	c.173-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001277150.1
NQO2	NM_001290222.2 linkuse as main transcript	c.173-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001277151.1
NQO2	NM_001318940.2 linkuse as main transcript	c.173-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001305869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11 linkuse as main transcript	c.173-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000904.6	ENSP00000369822	P1

Frequencies

GnomAD3 genomes

AF:

0.00471

AC:

717

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00509

AC:

1278

AN:

251202

Hom.:

AF XY:

0.00417

AC XY:

566

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0153

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00167

AC:

2436

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1106

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0253

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0197

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00273

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00470

AC:

716

AN:

152196

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

454

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.0366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0152

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000637

Hom.:

Bravo

AF:

0.00636

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.87

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.042

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over