12-121440856-C-T

Variant names:

• chr12-121440856-C-T
• rs1064951
• NM_032590.5:c.3570G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_032590.5(KDM2B):​c.3570G>A​(p.Gln1190Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,502 control chromosomes in the GnomAD database, including 122,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (9683 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112916 hom.)
• Consequence: KDM2B NM_032590.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.30
• Publications: 23 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=-0.37).
• BP6: Variant 12-121440856-C-T is Benign according to our data. Variant chr12-121440856-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060938.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM2B	NM_032590.5	MANE Select	c.3570G>A	p.Gln1190Gln	synonymous	Exon 21 of 23	NP_115979.3
	KDM2B	NM_001439014.1		c.3666G>A	p.Gln1222Gln	synonymous	Exon 21 of 23	NP_001425943.1
	KDM2B	NM_001439015.1		c.3666G>A	p.Gln1222Gln	synonymous	Exon 21 of 24	NP_001425944.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM2B	ENST00000377071.9	TSL:1 MANE Select	c.3570G>A	p.Gln1190Gln	synonymous	Exon 21 of 23	ENSP00000366271.3	Q8NHM5-1
	KDM2B	ENST00000543025.5	TSL:1	n.*1566-10387G>A		intron	N/A	ENSP00000438138.1	F5H0A1
	KDM2B	ENST00000717755.1		c.3585G>A	p.Gln1195Gln	synonymous	Exon 23 of 25	ENSP00000520643.1	A0ABB0MV58

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52173 AN: 151980 Hom.: 9682 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.353

GnomAD2 exomes AF: 0.392 AC: 97424 AN: 248616 AF XY: 0.387

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.473

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.512

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.389 AC: 568348 AN: 1461404 Hom.: 112916 Cov.: 43 AF XY: 0.386 AC XY: 280924 AN XY: 726988

African (AFR) AF: 0.191 AC: 6389 AN: 33466

American (AMR) AF: 0.464 AC: 20722 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 10145 AN: 26122

East Asian (EAS) AF: 0.418 AC: 16609 AN: 39698

South Asian (SAS) AF: 0.325 AC: 28043 AN: 86250

European-Finnish (FIN) AF: 0.504 AC: 26879 AN: 53350

Middle Eastern (MID) AF: 0.263 AC: 1514 AN: 5762

European-Non Finnish (NFE) AF: 0.391 AC: 435124 AN: 1111704

Other (OTH) AF: 0.380 AC: 22923 AN: 60362

GnomAD4 genome AF: 0.343 AC: 52200 AN: 152098 Hom.: 9683 Cov.: 32 AF XY: 0.347 AC XY: 25774 AN XY: 74340

African (AFR) AF: 0.201 AC: 8349 AN: 41518

American (AMR) AF: 0.382 AC: 5844 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3468

East Asian (EAS) AF: 0.434 AC: 2242 AN: 5166

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5566 AN: 10580

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26143 AN: 67946

Other (OTH) AF: 0.350 AC: 741 AN: 2116

Alfa AF: 0.360 Hom.: 13721

Bravo AF: 0.329

Asia WGS AF: 0.372 AC: 1289 AN: 3478

EpiCase AF: 0.365

EpiControl AF: 0.362

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KDM2B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.8
DANN	Benign	0.72
PhyloP100		1.3
Mutation Taster		=99/1	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: rs1064951; hg19: chr12-121878659; COSMIC: COSV65638622; COSMIC: COSV65638622;