rs796065033
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PM4PP5_Very_Strong
The NM_000433.4(NCF2):c.55_63delAAGAAGGAC(p.Lys19_Asp21del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000186 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. K19K) has been classified as Likely benign.
Frequency
Consequence
NM_000433.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NCF2 | NM_000433.4 | c.55_63delAAGAAGGAC | p.Lys19_Asp21del | conservative_inframe_deletion | Exon 1 of 15 | ENST00000367535.8 | NP_000424.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251460Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135902
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461890Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 Pathogenic:2
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This variant, c.55_63del, results in the deletion of 3 amino acid(s) of the NCF2 protein (p.Lys19_Asp21del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs796065033, gnomAD 0.003%). This variant has been observed in individual(s) with chronic granulomatous disease (PMID: 10498624, 10598813, 18625437; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2245). For these reasons, this variant has been classified as Pathogenic. -
not provided Pathogenic:1
In-frame deletion of 3 amino acids in a non-repeat region; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 18625437, 20167518, 10598813, 10498624, 32040803) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at