chr10-102396271-G-A
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001322934.2(NFKB2):c.40G>A(p.Glu14Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000841 in 1,612,586 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 4 hom., cov: 31)
Exomes 𝑓: 0.00051 ( 3 hom. )
Consequence
NFKB2
NM_001322934.2 missense
NM_001322934.2 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 4.74
Genes affected
NFKB2 (HGNC:7795): (nuclear factor kappa B subunit 2) This gene encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The protein encoded by this gene can function as both a transcriptional activator or repressor depending on its dimerization partner. The p100 full-length protein is co-translationally processed into a p52 active form. Chromosomal rearrangements and translocations of this locus have been observed in B cell lymphomas, some of which may result in the formation of fusion proteins. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NFKB2. . Gene score misZ 3.9376 (greater than the threshold 3.09). Trascript score misZ 3.5752 (greater than threshold 3.09). GenCC has associacion of gene with common variable immunodeficiency, deficiency in anterior pituitary function - variable immunodeficiency syndrome, immunodeficiency, common variable, 10.
BP4
Computational evidence support a benign effect (MetaRNN=0.006150514).
BP6
Variant 10-102396271-G-A is Benign according to our data. Variant chr10-102396271-G-A is described in ClinVar as [Benign]. Clinvar id is 474786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102396271-G-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00405 (617/152224) while in subpopulation AFR AF= 0.0136 (566/41538). AF 95% confidence interval is 0.0127. There are 4 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 617 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFKB2 | NM_001322934.2 | c.40G>A | p.Glu14Lys | missense_variant | 3/23 | ENST00000661543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFKB2 | ENST00000661543.1 | c.40G>A | p.Glu14Lys | missense_variant | 3/23 | NM_001322934.2 | P5 |
Frequencies
GnomAD3 genomes AF: 0.00403 AC: 613AN: 152106Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00119 AC: 298AN: 249404Hom.: 2 AF XY: 0.000902 AC XY: 122AN XY: 135302
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GnomAD4 exome AF: 0.000506 AC: 739AN: 1460362Hom.: 3 Cov.: 33 AF XY: 0.000467 AC XY: 339AN XY: 726134
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GnomAD4 genome AF: 0.00405 AC: 617AN: 152224Hom.: 4 Cov.: 31 AF XY: 0.00388 AC XY: 289AN XY: 74420
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Immunodeficiency, common variable, 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 24, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;D;.;.
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;.;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N;.;N
REVEL
Benign
Sift
Benign
.;T;T;.;T
Sift4G
Benign
T;D;D;T;D
Polyphen
0.12
.;.;B;.;.
Vest4
0.31, 0.32, 0.31
MVP
MPC
1.4
ClinPred
T
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at