chr10-102397954-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001322934.2(NFKB2):c.662-27T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,608,700 control chromosomes in the GnomAD database, including 40,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.25 ( 5353 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35621 hom. )

Consequence

NFKB2
NM_001322934.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.430

Publications

54 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
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 -14 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-102397954-T-G is Benign according to our data. Variant chr10-102397954-T-G is described in ClinVar as Benign. ClinVar VariationId is 2628219.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFKB2	NM_001322934.2	MANE Select	c.662-27T>G	intron	N/A	NP_001309863.1	Q00653-1
NFKB2	NM_001077494.3		c.662-27T>G	intron	N/A	NP_001070962.1	Q00653-1
NFKB2	NM_001261403.3		c.662-27T>G	intron	N/A	NP_001248332.1	Q00653-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFKB2	ENST00000661543.1	MANE Select	c.662-27T>G	intron	N/A	ENSP00000499294.1	Q00653-1
NFKB2	ENST00000369966.8	TSL:1	c.662-27T>G	intron	N/A	ENSP00000358983.3	Q00653-1
NFKB2	ENST00000189444.11	TSL:1	c.662-27T>G	intron	N/A	ENSP00000189444.6	Q00653-4

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38308

AN:

152060

Hom.:

5335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.227

GnomAD2 exomes

AF:

0.233

AC:

58041

AN:

249136

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.363

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.216

AC:

314470

AN:

1456522

Hom.:

35621

Cov.:

AF XY:

0.216

AC XY:

156333

AN XY:

724640

show subpopulations

African (AFR)

AF:

0.361

AC:

12034

AN:

33352

American (AMR)

AF:

0.228

AC:

10181

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

6518

AN:

26104

East Asian (EAS)

AF:

0.373

AC:

14781

AN:

39634

South Asian (SAS)

AF:

0.240

AC:

20646

AN:

86120

European-Finnish (FIN)

AF:

0.193

AC:

10295

AN:

53376

Middle Eastern (MID)

AF:

0.184

AC:

1052

AN:

5724

European-Non Finnish (NFE)

AF:

0.204

AC:

225361

AN:

1107390

Other (OTH)

AF:

0.226

AC:

13602

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13153

26306

39460

52613

65766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8116

16232

24348

32464

40580

<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:

0.252

AC:

38364

AN:

152178

Hom.:

5353

Cov.:

AF XY:

0.249

AC XY:

18556

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.357

AC:

14829

AN:

41494

American (AMR)

AF:

0.227

AC:

3470

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3470

East Asian (EAS)

AF:

0.349

AC:

1812

AN:

5186

South Asian (SAS)

AF:

0.254

AC:

1226

AN:

4820

European-Finnish (FIN)

AF:

0.185

AC:

1958

AN:

10610

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13553

AN:

67992

Other (OTH)

AF:

0.227

AC:

480

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1461

2923

4384

5846

7307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.209

Hom.:

4781

Bravo

AF:

0.262

Asia WGS

AF:

0.318

AC:

1105

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

-0.43

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over