NM_032590.5:c.83_84delCA

Variant names:

• chr12-121580827-CTG-C
• rs575373073
• NM_032590.5:c.83_84delCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 4P and 12B. PVS1_Strong BP6_Very_Strong BS2

The NM_032590.5(KDM2B):​c.83_84delCA​(p.Thr28SerfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,614,044 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (19 hom.)
• Consequence: KDM2B NM_032590.5 frameshift
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.301
• Publications: 5 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-DT (HGNC:53287): (KDM2B divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 12 pathogenic variants in the truncated region.
• BP6: Variant 12-121580827-CTG-C is Benign according to our data. Variant chr12-121580827-CTG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 777690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 357 AD gene.

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.83_84delCA	p.Thr28SerfsTer8	frameshift	Exon 1 of 23	NP_115979.3
	KDM2B	NM_001439016.1		c.83_84delCA	p.Thr28SerfsTer8	frameshift	Exon 1 of 24	NP_001425945.1
	KDM2B	NM_001439017.1		c.83_84delCA	p.Thr28SerfsTer8	frameshift	Exon 2 of 24	NP_001425946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM2B	ENST00000377071.9	TSL:1 MANE Select	c.83_84delCA	p.Thr28SerfsTer8	frameshift	Exon 1 of 23	ENSP00000366271.3	Q8NHM5-1
	KDM2B	ENST00000538046.6	TSL:1	c.83_84delCA	p.Thr28SerfsTer8	frameshift	Exon 1 of 10	ENSP00000474307.1	S4R3G4
	KDM2B	ENST00000543025.5	TSL:1	n.83_84delCA		non_coding_transcript_exon	Exon 1 of 13	ENSP00000438138.1	F5H0A1

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 359 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00404

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00284 AC: 709 AN: 249450 AF XY: 0.00296

Gnomad AFR exome AF: 0.000839

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00421

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00335 AC: 4892 AN: 1461748 Hom.: 19 AF XY: 0.00335 AC XY: 2435 AN XY: 727170

African (AFR) AF: 0.000747 AC: 25 AN: 33478

American (AMR) AF: 0.00123 AC: 55 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 71 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00357 AC: 308 AN: 86226

European-Finnish (FIN) AF: 0.00228 AC: 122 AN: 53418

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.00374 AC: 4154 AN: 1111942

Other (OTH) AF: 0.00243 AC: 147 AN: 60386

GnomAD4 genome AF: 0.00234 AC: 357 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74468

African (AFR) AF: 0.000578 AC: 24 AN: 41556

American (AMR) AF: 0.000850 AC: 13 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00404 AC: 275 AN: 68020

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00353 Hom.: 0

Bravo AF: 0.00216

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00344

EpiControl AF: 0.00320

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=147/53	disease causing (fs/PTC)

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: rs575373073; hg19: chr12-122018732; COSMIC: COSV65641530; COSMIC: COSV65641530;