rs13306581
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000433.4(NCF2):c.836C>T(p.Thr279Met) variant causes a missense change. The variant allele was found at a frequency of 0.00122 in 1,614,094 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T279T) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 26 hom. )
Consequence
NCF2
NM_000433.4 missense
NM_000433.4 missense
Scores
2
7
7
Clinical Significance
Conservation
PhyloP100: 4.62
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]
SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010832995).
BP6
?
Variant 1-183567223-G-A is Benign according to our data. Variant chr1-183567223-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 379274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-183567223-G-A is described in Lovd as [Benign]. Variant chr1-183567223-G-A is described in Lovd as [Likely_benign]. Variant chr1-183567223-G-A is described in Lovd as [Pathogenic].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00134 (204/152208) while in subpopulation EAS AF= 0.0267 (138/5178). AF 95% confidence interval is 0.023. There are 1 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 26 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF2 | NM_000433.4 | c.836C>T | p.Thr279Met | missense_variant | 8/15 | ENST00000367535.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF2 | ENST00000367535.8 | c.836C>T | p.Thr279Met | missense_variant | 8/15 | 1 | NM_000433.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00135 AC: 206AN: 152090Hom.: 1 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
206
AN:
152090
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00216 AC: 541AN: 250720Hom.: 7 AF XY: 0.00196 AC XY: 266AN XY: 135500
GnomAD3 exomes
AF:
AC:
541
AN:
250720
Hom.:
AF XY:
AC XY:
266
AN XY:
135500
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00121 AC: 1762AN: 1461886Hom.: 26 Cov.: 32 AF XY: 0.00123 AC XY: 897AN XY: 727242
GnomAD4 exome
AF:
AC:
1762
AN:
1461886
Hom.:
Cov.:
32
AF XY:
AC XY:
897
AN XY:
727242
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00134 AC: 204AN: 152208Hom.: 1 Cov.: 32 AF XY: 0.00159 AC XY: 118AN XY: 74418
GnomAD4 genome
?
AF:
AC:
204
AN:
152208
Hom.:
Cov.:
32
AF XY:
AC XY:
118
AN XY:
74418
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
7
ExAC
?
AF:
AC:
277
Asia WGS
AF:
AC:
72
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | NCF2: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2020 | This variant is associated with the following publications: (PMID: 29560547, 31180159) - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 18, 2022 | - - |
NCF2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 09, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;.
Polyphen
1.0
.;.;D;D;.
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
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