rs796065030
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000433.4(NCF2):c.399_400dupGA(p.Lys134ArgfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
NCF2
NM_000433.4 frameshift
NM_000433.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.817
Publications
1 publications found
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]
SMG7 Gene-Disease associations (from GenCC):
- autoimmune diseaseInheritance: AD Classification: NO_KNOWN Submitted by: Illumina
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-183574587-T-TTC is Pathogenic according to our data. Variant chr1-183574587-T-TTC is described in ClinVar as Pathogenic. ClinVar VariationId is 2239.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000433.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NCF2 | MANE Select | c.399_400dupGA | p.Lys134ArgfsTer12 | frameshift | Exon 4 of 15 | NP_000424.2 | P19878-1 | ||
| NCF2 | c.399_400dupGA | p.Lys134ArgfsTer12 | frameshift | Exon 5 of 16 | NP_001121123.1 | P19878-1 | |||
| NCF2 | c.399_400dupGA | p.Lys134ArgfsTer12 | frameshift | Exon 5 of 15 | NP_001397824.1 | A0A8V8TMB9 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NCF2 | TSL:1 MANE Select | c.399_400dupGA | p.Lys134ArgfsTer12 | frameshift | Exon 4 of 15 | ENSP00000356505.4 | P19878-1 | ||
| NCF2 | TSL:1 | c.399_400dupGA | p.Lys134ArgfsTer12 | frameshift | Exon 5 of 16 | ENSP00000356506.1 | P19878-1 | ||
| NCF2 | c.399_400dupGA | p.Lys134ArgfsTer12 | frameshift | Exon 4 of 16 | ENSP00000616354.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727242 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461880
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727242
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
1
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112002
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.