rs35012521
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000433.4(NCF2):c.1256A>T(p.Asn419Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00794 in 1,614,052 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N419Y) has been classified as Benign.
Frequency
Consequence
NM_000433.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NCF2 | NM_000433.4 | c.1256A>T | p.Asn419Ile | missense_variant | Exon 13 of 15 | ENST00000367535.8 | NP_000424.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00537 AC: 817AN: 152072Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00552 AC: 1387AN: 251352Hom.: 6 AF XY: 0.00573 AC XY: 778AN XY: 135834
GnomAD4 exome AF: 0.00821 AC: 12000AN: 1461862Hom.: 72 Cov.: 32 AF XY: 0.00819 AC XY: 5956AN XY: 727234
GnomAD4 genome AF: 0.00537 AC: 817AN: 152190Hom.: 6 Cov.: 32 AF XY: 0.00503 AC XY: 374AN XY: 74404
ClinVar
Submissions by phenotype
not specified Benign:3
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not provided Benign:3
This variant is associated with the following publications: (PMID: 23821607, 16937026, 27884173, 26764160, 27535533, 29454792, 24931457) -
NCF2: BP4, BS1, BS2 -
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Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 Benign:3
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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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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Developmental and epileptic encephalopathy, 28 Benign:1
The homozygous p.Asn419Ile variant in NCF2 has been identified in a Tunisian individual with chronic granulomatous disease (PMID: 16937026), individuals without chronic granulomatous disease (PMID: 23821607), and has been identified in >1% of South Asian chromosomes and 6 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive chronic granulomatous disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at