Variant 12-121580827-CTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 4P and 12B. PVS1_StrongBP6_Very_StrongBS2

The ENST00000377071.9(KDM2B):c.83_84del(p.Thr28SerfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,614,044 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 19 hom. )

Consequence

KDM2B
ENST00000377071.9 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.301

Variant links:

Genes affected

KDM2B (HGNC:13610): (lysine demethylase 2B) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

KDM2B links:

KDM2B-DT (HGNC:53287): (KDM2B divergent transcript)

KDM2B-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.

BP6

Variant 12-121580827-CTG-C is Benign according to our data. Variant chr12-121580827-CTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 777690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 357 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM2B	NM_032590.5 linkuse as main transcript	c.83_84del	p.Thr28SerfsTer8	frameshift_variant	1/23	ENST00000377071.9	NP_115979.3
KDM2B-DT	NR_183427.1 linkuse as main transcript	n.319_320del		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM2B	ENST00000377071.9 linkuse as main transcript	c.83_84del	p.Thr28SerfsTer8	frameshift_variant	1/23	1	NM_032590.5	ENSP00000366271	P1	Q8NHM5-1
KDM2B-DT	ENST00000541574.1 linkuse as main transcript	n.38_39del		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00404

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00284

AC:

709

AN:

249450

Hom.:

AF XY:

0.00296

AC XY:

401

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00421

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00335

AC:

4892

AN:

1461748

Hom.:

AF XY:

0.00335

AC XY:

2435

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00357

Gnomad4 FIN exome

AF:

0.00228

Gnomad4 NFE exome

AF:

0.00374

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00234

AC:

357

AN:

152296

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00404

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.00216

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	KDM2B: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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