12-121459249-T-C

Variant names:

• chr12-121459249-T-C
• rs7134248
• NM_032590.5:c.1735-5905A>G

Variant summary

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

The NM_032590.5(KDM2B):​c.1735-5905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,966 control chromosomes in the GnomAD database, including 23,920 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 0.56 (23920 hom., cov: 32)
• Consequence: KDM2B NM_032590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM2B	NM_032590.5	c.1735-5905A>G		intron_variant	Intron 12 of 22	ENST00000377071.9	NP_115979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM2B	ENST00000377071.9	c.1735-5905A>G		intron_variant	Intron 12 of 22	1	NM_032590.5	ENSP00000366271.3

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84672 AN: 151848 Hom.: 23889 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.558 AC: 84754 AN: 151966 Hom.: 23920 Cov.: 32 AF XY: 0.565 AC XY: 41989 AN XY: 74264

African (AFR) AF: 0.622 AC: 25757 AN: 41434

American (AMR) AF: 0.508 AC: 7763 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3484 AN: 5156

South Asian (SAS) AF: 0.639 AC: 3074 AN: 4814

European-Finnish (FIN) AF: 0.649 AC: 6850 AN: 10562

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.507 AC: 34443 AN: 67948

Other (OTH) AF: 0.533 AC: 1122 AN: 2106

Alfa AF: 0.536 Hom.: 3128

Bravo AF: 0.549

Asia WGS AF: 0.645 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.14
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: rs7134248; hg19: chr12-121897052;