chr10-102395967-G-C

Variant names:

• chr10-102395967-G-C
• NM_001322934.2:c.8G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001322934.2(NFKB2):​c.8G>C​(p.Ser3Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NFKB2 NM_001322934.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.117

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06473601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2	c.8G>C	p.Ser3Thr	missense_variant	Exon 2 of 23	ENST00000661543.1	NP_001309863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1	c.8G>C	p.Ser3Thr	missense_variant	Exon 2 of 23		NM_001322934.2	ENSP00000499294.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8G>C (p.S3T) alteration is located in exon 2 (coding exon 1) of the NFKB2 gene. This alteration results from a G to C substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.075	T;.;T;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.44	T;T;T;.;.
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.065	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;L;.;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.50	.;N;N;.;N
REVEL	Benign	0.041
Sift	Benign	0.091	.;T;T;.;T
Sift4G	Pathogenic	0.0	D;T;T;T;T
Polyphen		0.0080	.;.;B;.;.
Vest4		0.28, 0.26, 0.28
MutPred		0.16		Loss of disorder (P = 0.086);Loss of disorder (P = 0.086);Loss of disorder (P = 0.086);Loss of disorder (P = 0.086);Loss of disorder (P = 0.086);
MVP		0.45
MPC		1.2
ClinPred		0.097	T
GERP RS		1.6
Varity_R		0.074
gMVP		0.72

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: chr10-104155724;