10-102398844-G-T

Variant names:

• chr10-102398844-G-T
• NM_001322934.2:c.1097G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001322934.2(NFKB2):​c.1097G>T​(p.Gly366Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,420 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NFKB2 NM_001322934.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.13

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2	c.1097G>T	p.Gly366Val	missense_variant	Exon 12 of 23	ENST00000661543.1	NP_001309863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1	c.1097G>T	p.Gly366Val	missense_variant	Exon 12 of 23		NM_001322934.2	ENSP00000499294.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1448420 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 719746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;T;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T;T;.
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.71
MutPred		0.34		Gain of phosphorylation at Y367 (P = 0.1368);Gain of phosphorylation at Y367 (P = 0.1368);Gain of phosphorylation at Y367 (P = 0.1368);
MVP		0.40
MPC		1.7
ClinPred		0.98	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104158601;