10-102401464-C-T

Variant names:

• chr10-102401464-C-T
• rs11191279
• NM_001322934.2:c.2239C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001322934.2(NFKB2):​c.2239C>T​(p.Leu747Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,613,894 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (13 hom., cov: 33)
  • Exomes 𝑓: 0.016 (238 hom.)
• Consequence: NFKB2 NM_001322934.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.896
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-102401464-C-T is Benign according to our data. Variant chr10-102401464-C-T is described in ClinVar as Benign. ClinVar VariationId is 474782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.896 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00986 (1501/152234) while in subpopulation NFE AF = 0.0165 (1123/67994). AF 95% confidence interval is 0.0157. There are 13 homozygotes in GnomAd4. There are 696 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1501 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322934.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKB2	NM_001322934.2	MANE Select	c.2239C>T	p.Leu747Leu	synonymous	Exon 20 of 23	NP_001309863.1
	NFKB2	NM_001077494.3		c.2239C>T	p.Leu747Leu	synonymous	Exon 20 of 23	NP_001070962.1
	NFKB2	NM_001261403.3		c.2239C>T	p.Leu747Leu	synonymous	Exon 19 of 22	NP_001248332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKB2	ENST00000661543.1	MANE Select	c.2239C>T	p.Leu747Leu	synonymous	Exon 20 of 23	ENSP00000499294.1
	NFKB2	ENST00000369966.8	TSL:1	c.2239C>T	p.Leu747Leu	synonymous	Exon 20 of 23	ENSP00000358983.3
	NFKB2	ENST00000189444.11	TSL:1	c.2239C>T	p.Leu747Leu	synonymous	Exon 20 of 23	ENSP00000189444.6

Frequencies

GnomAD3 genomes AF: 0.00987 AC: 1502 AN: 152118 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00348

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.0106 AC: 2636 AN: 249040 AF XY: 0.0106

Gnomad AFR exome AF: 0.00362

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0168

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.0155 AC: 22685 AN: 1461660 Hom.: 238 Cov.: 36 AF XY: 0.0150 AC XY: 10936 AN XY: 727140

African (AFR) AF: 0.00221 AC: 74 AN: 33480

American (AMR) AF: 0.00347 AC: 155 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 326 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00322 AC: 278 AN: 86256

European-Finnish (FIN) AF: 0.0128 AC: 681 AN: 53268

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5766

European-Non Finnish (NFE) AF: 0.0184 AC: 20439 AN: 1111956

Other (OTH) AF: 0.0119 AC: 716 AN: 60390

GnomAD4 genome AF: 0.00986 AC: 1501 AN: 152234 Hom.: 13 Cov.: 33 AF XY: 0.00935 AC XY: 696 AN XY: 74432

African (AFR) AF: 0.00347 AC: 144 AN: 41546

American (AMR) AF: 0.00360 AC: 55 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4824

European-Finnish (FIN) AF: 0.00951 AC: 101 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0165 AC: 1123 AN: 67994

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.0141 Hom.: 20

Bravo AF: 0.00981

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0155

EpiControl AF: 0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency, common variable, 10 Benign:2

Nov 01, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.76
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11191279; hg19: chr10-104161221; COSMIC: COSV50068249; COSMIC: COSV50068249;