Variant chr10-102402039-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001322934.2(NFKB2):c.2467-9T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,569,874 control chromosomes in the GnomAD database, including 1,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 403 hom., cov: 33)

Exomes 𝑓: 0.022 ( 729 hom. )

Consequence

NFKB2
NM_001322934.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0004057

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.418

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-102402039-T-A is Benign according to our data. Variant chr10-102402039-T-A is described in ClinVar as [Benign]. Clinvar id is 403235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKB2	NM_001322934.2 linkuse as main transcript	c.2467-9T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000661543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKB2	ENST00000661543.1 linkuse as main transcript	c.2467-9T>A		splice_polypyrimidine_tract_variant, intron_variant			NM_001322934.2	P5	Q00653-1

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7626

AN:

152186

Hom.:

402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0250

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0422

GnomAD3 exomes

AF:

0.0264

AC:

4664

AN:

176834

Hom.:

158

AF XY:

0.0258

AC XY:

2434

AN XY:

94488

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0361

Gnomad EAS exome

AF:

0.000469

Gnomad SAS exome

AF:

0.0343

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.0212

Gnomad OTH exome

AF:

0.0237

GnomAD4 exome

AF:

0.0224

AC:

31738

AN:

1417570

Hom.:

729

Cov.:

AF XY:

0.0225

AC XY:

15776

AN XY:

701110

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0361

Gnomad4 EAS exome

AF:

0.000375

Gnomad4 SAS exome

AF:

0.0315

Gnomad4 FIN exome

AF:

0.00372

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0302

GnomAD4 genome

AF:

0.0502

AC:

7646

AN:

152304

Hom.:

403

Cov.:

AF XY:

0.0479

AC XY:

3567

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.0354

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.0196

Gnomad4 OTH

AF:

0.0417

Alfa

AF:

0.0291

Hom.:

Bravo

AF:

0.0551

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency, common variable, 10

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.1

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00041

dbscSNV1_RF

Benign

0.090

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over