12-121580856-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032590.5(KDM2B):c.56A>G(p.His19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00724 in 1,614,140 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 58 hom. )

Consequence

KDM2B
NM_032590.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.157

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036444366).

BP6

Variant 12-121580856-T-C is Benign according to our data. Variant chr12-121580856-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 770235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-121580856-T-C is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 914 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM2B	NM_032590.5 link	c.56A>G	p.His19Arg	missense_variant	Exon 1 of 23	ENST00000377071.9	NP_115979.3	Q8NHM5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM2B	ENST00000377071.9 link	c.56A>G	p.His19Arg	missense_variant	Exon 1 of 23	1	NM_032590.5	ENSP00000366271.3		Q8NHM5-1

Frequencies

GnomAD3 genomes

AF:

0.00600

AC:

914

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00941

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00532

AC:

1327

AN:

249476

Hom.:

AF XY:

0.00535

AC XY:

724

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.00409

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00612

Gnomad NFE exome

AF:

0.00840

Gnomad OTH exome

AF:

0.00611

GnomAD4 exome

AF:

0.00737

AC:

10767

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

5175

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00429

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000916

Gnomad4 FIN exome

AF:

0.00623

Gnomad4 NFE exome

AF:

0.00865

Gnomad4 OTH exome

AF:

0.00747

GnomAD4 genome

AF:

0.00600

AC:

914

AN:

152360

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

430

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.00941

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00678

Hom.:

Bravo

AF:

0.00572

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00188

AC:

ESP6500EA

AF:

0.00673

AC:

ExAC

AF:

0.00532

AC:

643

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00824

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KDM2B: BP4, BS2 -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KDM2B-related disorder

Benign:1

Mar 14, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.068

T;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.17

N;.;.

REVEL

Benign

0.055

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;T;T

Polyphen

0.0

B;.;.

Vest4

0.39

MVP

0.34

MPC

1.3

ClinPred

0.029

GERP RS

-0.98

Varity_R

0.28

gMVP

0.15

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