12-121440856-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_032590.5(KDM2B):c.3570G>A(p.Gln1190=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9683 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112916 hom.)
• Consequence: KDM2B NM_032590.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

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]

ACMG classification

Verdict is Benign. Variant got -13 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 id is 3060938.Status of the report is criteria_provided_single_submitter, 1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM2B	NM_032590.5	c.3570G>A	p.Gln1190=	synonymous_variant	21/23	ENST00000377071.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM2B	ENST00000377071.9	c.3570G>A	p.Gln1190=	synonymous_variant	21/23	1	NM_032590.5	P1

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

GnomAD3 exomes AF: 0.392 AC: 97424 AN: 248616 Hom.: 20001 AF XY: 0.387 AC XY: 52224 AN XY: 134924

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 SAS exome AF: 0.326

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

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.380

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

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.350

Alfa AF: 0.364 Hom.: 10869

Bravo AF: 0.329

Asia WGS AF: 0.372 AC: 1289 AN: 3478

EpiCase AF: 0.365

EpiControl AF: 0.362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KDM2B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as 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
BayesDel_noAF	Benign	-0.37
Cadd	Benign	8.8
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs1064951; hg19: chr12-121878659; COSMIC: COSV65638622; COSMIC: COSV65638622;