10-102395993-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001322934.2(NFKB2):c.21+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,612,044 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (16 hom.)
• Consequence: NFKB2 NM_001322934.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.657

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-102395993-G-A is Benign according to our data. Variant chr10-102395993-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 993820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0028 (426/152200) while in subpopulation NFE AF= 0.00496 (337/67986). AF 95% confidence interval is 0.00452. There are 1 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 426 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKB2	NM_001322934.2	c.21+13G>A		intron_variant		ENST00000661543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKB2	ENST00000661543.1	c.21+13G>A		intron_variant			NM_001322934.2	P5

Frequencies

GnomAD3 genomes AF: 0.00280 AC: 426 AN: 152082 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00496

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00232 AC: 574 AN: 247494 Hom.: 2 AF XY: 0.00217 AC XY: 292 AN XY: 134616

Gnomad AFR exome AF: 0.000843

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000654

Gnomad NFE exome AF: 0.00456

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00462 AC: 6742 AN: 1459844 Hom.: 16 Cov.: 32 AF XY: 0.00448 AC XY: 3253 AN XY: 726386

Gnomad4 AFR exome AF: 0.000806

Gnomad4 AMR exome AF: 0.000783

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.000913

Gnomad4 NFE exome AF: 0.00571

Gnomad4 OTH exome AF: 0.00449

GnomAD4 genome AF: 0.00280 AC: 426 AN: 152200 Hom.: 1 Cov.: 31 AF XY: 0.00247 AC XY: 184 AN XY: 74420

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00496

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00236 Hom.: 0

Bravo AF: 0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency, common variable, 10 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 08, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	7.7
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs199513883; hg19: chr10-104155750;