10-102397297-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001322934.2(NFKB2):c.396-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

NFKB2
NM_001322934.2 splice_region, intron

Scores

Splicing: ADA: 0.00003203

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.445

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-102397297-C-T is Benign according to our data. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-102397297-C-T is described in CliVar as Likely_benign. Clinvar id is 541633.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2 link	c.396-5C>T		splice_region_variant, intron_variant	Intron 6 of 22	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.396-5C>T		splice_region_variant, intron_variant	Intron 6 of 22		NM_001322934.2	ENSP00000499294.1		Q00653-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249286

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461416

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000990

AC:

AN:

1111648

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency, common variable, 10

Benign:1

Jan 24, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.4

(source)

DANN

Benign

0.44

PhyloP100

-0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.052

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

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over