NM_032590.5:c.1648-5717G>C

Variant names:

• chr12-121500382-C-G
• rs10849893
• NM_032590.5:c.1648-5717G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032590.5(KDM2B):​c.1648-5717G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,192 control chromosomes in the GnomAD database, including 8,595 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (8595 hom., cov: 32)
• Consequence: KDM2B NM_032590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM2B	NM_032590.5	MANE Select	c.1648-5717G>C		intron	N/A	NP_115979.3
	KDM2B	NM_001439014.1		c.1744-5717G>C		intron	N/A	NP_001425943.1
	KDM2B	NM_001439015.1		c.1744-5717G>C		intron	N/A	NP_001425944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM2B	ENST00000377071.9	TSL:1 MANE Select	c.1648-5717G>C		intron	N/A	ENSP00000366271.3
	KDM2B	ENST00000538046.6	TSL:1	c.1378-5717G>C		intron	N/A	ENSP00000474307.1
	KDM2B	ENST00000543025.5	TSL:1	n.*1254-5717G>C		intron	N/A	ENSP00000438138.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46009 AN: 152074 Hom.: 8588 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 46016 AN: 152192 Hom.: 8595 Cov.: 32 AF XY: 0.301 AC XY: 22407 AN XY: 74394

African (AFR) AF: 0.0830 AC: 3450 AN: 41574

American (AMR) AF: 0.411 AC: 6276 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1105 AN: 5180

South Asian (SAS) AF: 0.329 AC: 1588 AN: 4824

European-Finnish (FIN) AF: 0.264 AC: 2793 AN: 10576

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27901 AN: 67980

Other (OTH) AF: 0.359 AC: 758 AN: 2110

Alfa AF: 0.339 Hom.: 1223

Bravo AF: 0.303

Asia WGS AF: 0.283 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.70
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10849893; hg19: chr12-121938185;