GeneBe

NM_001322934.2:c.1386C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001322934.2(NFKB2):​c.1386C>A​(p.Leu462Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L462L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

NFKB2
NM_001322934.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

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: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP7
Synonymous conserved (PhyloP=-1.01 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFKB2NM_001322934.2 linkc.1386C>A p.Leu462Leu synonymous_variant Exon 14 of 23 ENST00000661543.1 NP_001309863.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NFKB2ENST00000661543.1 linkc.1386C>A p.Leu462Leu synonymous_variant Exon 14 of 23 NM_001322934.2 ENSP00000499294.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.20e-7
AC:
1
AN:
1389422
Hom.:
0
Cov.:
35
AF XY:
0.00000146
AC XY:
1
AN XY:
684634
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
31140
American (AMR)
AF:
0.00
AC:
0
AN:
34704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24890
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35342
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78716
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46314
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5620
European-Non Finnish (NFE)
AF:
9.30e-7
AC:
1
AN:
1075184
Other (OTH)
AF:
0.00
AC:
0
AN:
57512
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.22
CADD
Benign
4.7
DANN
Benign
0.94
PhyloP100
-1.0

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: rs762807587; hg19: chr10-104159392; API