rs200227171
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_001322934.2(NFKB2):c.1736G>A(p.Arg579His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000689 in 1,612,766 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R579C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001322934.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFKB2 | NM_001322934.2 | c.1736G>A | p.Arg579His | missense_variant | 16/23 | ENST00000661543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFKB2 | ENST00000661543.1 | c.1736G>A | p.Arg579His | missense_variant | 16/23 | NM_001322934.2 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000644 AC: 98AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000955 AC: 236AN: 247026Hom.: 2 AF XY: 0.000991 AC XY: 133AN XY: 134274
GnomAD4 exome AF: 0.000694 AC: 1014AN: 1460468Hom.: 5 Cov.: 34 AF XY: 0.000764 AC XY: 555AN XY: 726602
GnomAD4 genome ? AF: 0.000637 AC: 97AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53AN XY: 74466
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 10 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | NFKB2 NM_001077494.3 exon 16 p.Arg579His (c.1736G>A): This variant has not been reported in the literature but is present in 0.1% (41/30766) of South Asian alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs200227171). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
NFKB2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 03, 2022 | 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | NFKB2: BS1, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at