10-102399458-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001322934.2(NFKB2):​c.1288C>A​(p.Pro430Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P430S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

NFKB2
NM_001322934.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

Publications

0 publications found
Variant links:
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]
NFKB2 Gene-Disease associations (from GenCC):
  • immunodeficiency, common variable, 10
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • common variable immunodeficiency
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • deficiency in anterior pituitary function - variable immunodeficiency syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.105917394).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFKB2NM_001322934.2 linkc.1288C>A p.Pro430Thr missense_variant Exon 13 of 23 ENST00000661543.1 NP_001309863.1 Q00653-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NFKB2ENST00000661543.1 linkc.1288C>A p.Pro430Thr missense_variant Exon 13 of 23 NM_001322934.2 ENSP00000499294.1 Q00653-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.38e-7
AC:
1
AN:
1355796
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
665192
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28674
American (AMR)
AF:
0.00
AC:
0
AN:
30114
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22738
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33768
South Asian (SAS)
AF:
0.00
AC:
0
AN:
75232
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46388
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5214
European-Non Finnish (NFE)
AF:
9.45e-7
AC:
1
AN:
1057820
Other (OTH)
AF:
0.00
AC:
0
AN:
55848
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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
5.0
DANN
Benign
0.75
DEOGEN2
Benign
0.10
.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.086
N
LIST_S2
Benign
0.70
T;T;.
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.7
L;L;L
PhyloP100
1.2
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
0.37
N;N;N
REVEL
Benign
0.077
Sift
Benign
0.39
T;T;T
Sift4G
Benign
0.58
T;T;T
Polyphen
0.011
.;B;.
Vest4
0.23
MutPred
0.16
Gain of phosphorylation at P430 (P = 0.0177);Gain of phosphorylation at P430 (P = 0.0177);Gain of phosphorylation at P430 (P = 0.0177);
MVP
0.34
MPC
0.69
ClinPred
0.085
T
GERP RS
3.6
Varity_R
0.021
gMVP
0.30
Mutation Taster
=99/1
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs202001697; hg19: chr10-104159215; API