10-102397970-C-T

Variant names:

Variant summary

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

The NM_001322934.2(NFKB2):c.662-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,613,662 control chromosomes in the GnomAD database, including 762,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66287 hom., cov: 32)

Exomes 𝑓: 0.98 ( 695977 hom. )

Consequence

NFKB2
NM_001322934.2 intron

Scores

Splicing: ADA: 0.00009998

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0320

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=-0.65).

BP6

Variant 10-102397970-C-T is Benign according to our data. Variant chr10-102397970-C-T is described in ClinVar as [Benign]. Clinvar id is 403232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102397970-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2 link	c.662-11C>T		intron_variant	Intron 8 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.662-11C>T		intron_variant	Intron 8 of 22		NM_001322934.2	ENSP00000499294.1		Q00653-1

Frequencies

GnomAD3 genomes

AF:

0.929

AC:

141405

AN:

152138

Hom.:

66245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.797

Gnomad AMI

AF:

0.986

Gnomad AMR

AF:

0.967

Gnomad ASJ

AF:

0.964

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.970

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.980

Gnomad OTH

AF:

0.942

GnomAD3 exomes

AF:

0.968

AC:

241521

AN:

249528

Hom.:

117216

AF XY:

0.970

AC XY:

131337

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.789

Gnomad AMR exome

AF:

0.980

Gnomad ASJ exome

AF:

0.964

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.966

Gnomad FIN exome

AF:

0.997

Gnomad NFE exome

AF:

0.979

Gnomad OTH exome

AF:

0.974

GnomAD4 exome

AF:

0.975

AC:

1425421

AN:

1461406

Hom.:

695977

Cov.:

AF XY:

0.975

AC XY:

709223

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.786

Gnomad4 AMR exome

AF:

0.979

Gnomad4 ASJ exome

AF:

0.964

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.968

Gnomad4 FIN exome

AF:

0.996

Gnomad4 NFE exome

AF:

0.981

Gnomad4 OTH exome

AF:

0.965

GnomAD4 genome

AF:

0.929

AC:

141504

AN:

152256

Hom.:

66287

Cov.:

AF XY:

0.932

AC XY:

69420

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.797

Gnomad4 AMR

AF:

0.967

Gnomad4 ASJ

AF:

0.964

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.970

Gnomad4 FIN

AF:

0.997

Gnomad4 NFE

AF:

0.980

Gnomad4 OTH

AF:

0.943

Alfa

AF:

0.966

Hom.:

74232

Bravo

AF:

0.922

Asia WGS

AF:

0.976

AC:

3393

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Immunodeficiency, common variable, 10

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

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

-0.65

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0040

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

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