rs11574851

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001322934.2(NFKB2):c.2094C>T(p.Asn698Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 1,595,236 control chromosomes in the GnomAD database, including 2,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 152 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2035 hom. )

Consequence

NFKB2
NM_001322934.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.82

Publications

25 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

NFKB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-102401202-C-T is Benign according to our data. Variant chr10-102401202-C-T is described in ClinVar as Benign. ClinVar VariationId is 474781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2 link	c.2094C>T	p.Asn698Asn	synonymous_variant	Exon 19 of 23	ENST00000661543.1	NP_001309863.1	Q00653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1 link	c.2094C>T	p.Asn698Asn	synonymous_variant	Exon 19 of 23		NM_001322934.2	ENSP00000499294.1		Q00653-1

Frequencies

GnomAD3 genomes

AF:

0.0378

AC:

5750

AN:

152102

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00954

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.0650

Gnomad SAS

AF:

0.0379

Gnomad FIN

AF:

0.0508

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0485

GnomAD2 exomes

AF:

0.0426

AC:

10063

AN:

236134

AF XY:

0.0439

show subpopulations

Gnomad AFR exome

AF:

0.00841

Gnomad AMR exome

AF:

0.0259

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.0535

Gnomad FIN exome

AF:

0.0485

Gnomad NFE exome

AF:

0.0501

Gnomad OTH exome

AF:

0.0497

GnomAD4 exome

AF:

0.0514

AC:

74232

AN:

1443016

Hom.:

2035

Cov.:

AF XY:

0.0511

AC XY:

36599

AN XY:

715644

show subpopulations

African (AFR)

AF:

0.00844

AC:

278

AN:

32948

American (AMR)

AF:

0.0275

AC:

1178

AN:

42852

Ashkenazi Jewish (ASJ)

AF:

0.0398

AC:

989

AN:

24870

East Asian (EAS)

AF:

0.0814

AC:

3211

AN:

39444

South Asian (SAS)

AF:

0.0409

AC:

3441

AN:

84170

European-Finnish (FIN)

AF:

0.0479

AC:

2533

AN:

52852

Middle Eastern (MID)

AF:

0.0637

AC:

361

AN:

5664

European-Non Finnish (NFE)

AF:

0.0539

AC:

59347

AN:

1100726

Other (OTH)

AF:

0.0486

AC:

2894

AN:

59490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

4233

8465

12698

16930

21163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2330

4660

6990

9320

11650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0378

AC:

5750

AN:

152220

Hom.:

152

Cov.:

AF XY:

0.0378

AC XY:

2811

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00951

AC:

395

AN:

41538

American (AMR)

AF:

0.0334

AC:

511

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

155

AN:

3472

East Asian (EAS)

AF:

0.0649

AC:

336

AN:

5176

South Asian (SAS)

AF:

0.0379

AC:

183

AN:

4830

European-Finnish (FIN)

AF:

0.0508

AC:

539

AN:

10606

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0509

AC:

3464

AN:

67998

Other (OTH)

AF:

0.0508

AC:

107

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

286

572

857

1143

1429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0451

Hom.:

333

Bravo

AF:

0.0357

Asia WGS

AF:

0.0490

AC:

169

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency, common variable, 10

Benign:1

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.15

(source)

DANN

Benign

0.88

PhyloP100

-2.8

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over