10-102397954-T-G

Variant names:

• chr10-102397954-T-G
• rs7897947
• NM_001322934.2:c.662-27T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.430

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB2	NM_001322934.2	c.662-27T>G		intron_variant	Intron 8 of 22	ENST00000661543.1	NP_001309863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKB2	ENST00000661543.1	c.662-27T>G		intron_variant	Intron 8 of 22		NM_001322934.2	ENSP00000499294.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38308 AN: 152060 Hom.: 5335 Cov.: 32

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

GnomAD3 exomes AF: 0.233 AC: 58041 AN: 249136 Hom.: 7206 AF XY: 0.230 AC XY: 31103 AN XY: 135178

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 SAS exome AF: 0.240

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.: 29 AF XY: 0.216 AC XY: 156333 AN XY: 724640

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.373

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.252 AC: 38364 AN: 152178 Hom.: 5353 Cov.: 32 AF XY: 0.249 AC XY: 18556 AN XY: 74380

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.227

Alfa AF: 0.199 Hom.: 3146

Bravo AF: 0.262

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

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 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 35. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.62
BranchPoint Hunter		3.0

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: rs7897947; hg19: chr10-104157711;