Genetic Variant KDM2B:p.Lys23Glu (chr12-121580845-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032590.5(KDM2B):c.67A>G(p.Lys23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KDM2B
NM_032590.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.658

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08165002).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032590.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KDM2B	NM_032590.5	MANE Select	c.67A>G	p.Lys23Glu	missense	Exon 1 of 23	NP_115979.3
KDM2B	NM_001439016.1		c.67A>G	p.Lys23Glu	missense	Exon 1 of 24	NP_001425945.1
KDM2B	NM_001439017.1		c.67A>G	p.Lys23Glu	missense	Exon 2 of 24	NP_001425946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM2B	ENST00000377071.9	TSL:1 MANE Select	c.67A>G	p.Lys23Glu	missense	Exon 1 of 23	ENSP00000366271.3	Q8NHM5-1
KDM2B	ENST00000538046.6	TSL:1	c.67A>G	p.Lys23Glu	missense	Exon 1 of 10	ENSP00000474307.1	S4R3G4
KDM2B	ENST00000543025.5	TSL:1	n.67A>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000438138.1	F5H0A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.064

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.49

M_CAP

Benign

0.013

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

0.66

PrimateAI

Benign

0.47

PROVEAN

Benign

0.39

REVEL

Benign

0.045

Sift

Benign

0.030

Sift4G

Pathogenic

0.0

Polyphen

0.26

Vest4

0.34

MutPred

0.20

Loss of MoRF binding (P = 0.005)

MVP

0.17

MPC

1.4

ClinPred

0.45

GERP RS

3.3

PromoterAI

0.012

Neutral

(source)

Varity_R

0.086

gMVP

0.82

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over