chr1-183573252-T-C

Position:

chr1-183573252-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000433.4(NCF2):c.542A>G(p.Lys181Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,334 control chromosomes in the GnomAD database, including 191,513 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16273 hom., cov: 32)

Exomes 𝑓: 0.49 ( 175240 hom. )

Consequence

NCF2
NM_000433.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.615

Variant links:

Genes affected

NCF2 (HGNC:7661): (neutrophil cytosolic factor 2) This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein NADPH oxidase complex found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease, a disease that causes recurrent infections by catalase-positive organisms. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

NCF2 links:

NCF2 (HGNC:):

NCF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.207979E-5).

BP6

Variant 1-183573252-T-C is Benign according to our data. Variant chr1-183573252-T-C is described in ClinVar as [Benign]. Clinvar id is 256116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-183573252-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF2	NM_000433.4 linkuse as main transcript	c.542A>G	p.Lys181Arg	missense_variant	5/15	ENST00000367535.8	NP_000424.2	P19878-1A0A0S2Z457

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF2	ENST00000367535.8 linkuse as main transcript	c.542A>G	p.Lys181Arg	missense_variant	5/15	1	NM_000433.4	ENSP00000356505.4		P19878-1

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69469

AN:

151888

Hom.:

16259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.458

GnomAD3 exomes

AF:

0.499

AC:

125404

AN:

251436

Hom.:

32373

AF XY:

0.494

AC XY:

67184

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.359

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.623

Gnomad SAS exome

AF:

0.507

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.461

GnomAD4 exome

AF:

0.486

AC:

710885

AN:

1461330

Hom.:

175240

Cov.:

AF XY:

0.485

AC XY:

352498

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.352

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.392

Gnomad4 EAS exome

AF:

0.629

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.478

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.457

AC:

69503

AN:

152004

Hom.:

16273

Cov.:

AF XY:

0.461

AC XY:

34232

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.561

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.620

Gnomad4 SAS

AF:

0.511

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.473

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.469

Hom.:

44702

Bravo

AF:

0.461

TwinsUK

AF:

0.505

AC:

1872

ALSPAC

AF:

0.491

AC:

1891

ESP6500AA

AF:

0.359

AC:

1581

ESP6500EA

AF:

0.467

AC:

4012

ExAC

AF:

0.489

AC:

59412

Asia WGS

AF:

0.560

AC:

1943

AN:

3478

EpiCase

AF:

0.452

EpiControl

AF:

0.460

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 82% of patients studied by a panel of primary immunodeficiencies. Number of patients: 78. Only high quality variants are reported. -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.040

.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.15

T;.;T

MetaRNN

Benign

0.000032

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.084

Sift

Benign

0.91

T;T;T

Sift4G

Benign

0.86

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.050

MPC

0.25

ClinPred

0.0010

GERP RS

1.3

Varity_R

0.12

gMVP

0.34

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

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