rs397514332

chr10-102402138-C-Gchr10-102402138-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001322934.2(NFKB2):c.2557C>G(p.Arg853Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. R853Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NFKB2 NM_001322934.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, NFKB2
• BP4: Computational evidence support a benign effect (MetaRNN=0.07561013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKB2	NM_001322934.2	c.2557C>G	p.Arg853Gly	missense_variant	22/23	ENST00000661543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKB2	ENST00000661543.1	c.2557C>G	p.Arg853Gly	missense_variant	22/23		NM_001322934.2	P5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000533 AC: 1 AN: 187640 Hom.: 0 AF XY: 0.00000992 AC XY: 1 AN XY: 100806

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000730

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.89
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.79	T;T;.
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.20	.;B;.
Vest4		0.22
MutPred		0.22		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.31
MPC		0.79
ClinPred		0.068	T
GERP RS		2.0
Varity_R		0.10
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs397514332; hg19: chr10-104161895;