chr12-121580856-T-C

Variant names:

• chr12-121580856-T-C
• rs191586330
• NM_032590.5:c.56A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_032590.5(KDM2B):​c.56A>G​(p.His19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00724 in 1,614,140 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (58 hom.)
• Consequence: KDM2B NM_032590.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.157
• Publications: 11 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036444366).
• BP6: Variant 12-121580856-T-C is Benign according to our data. Variant chr12-121580856-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 770235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 914 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.56A>G	p.His19Arg	missense	Exon 1 of 23	NP_115979.3
	KDM2B	NM_001439016.1		c.56A>G	p.His19Arg	missense	Exon 1 of 24	NP_001425945.1
	KDM2B	NM_001439017.1		c.56A>G	p.His19Arg	missense	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.56A>G	p.His19Arg	missense	Exon 1 of 23	ENSP00000366271.3	Q8NHM5-1
	KDM2B	ENST00000538046.6	TSL:1	c.56A>G	p.His19Arg	missense	Exon 1 of 10	ENSP00000474307.1	S4R3G4
	KDM2B	ENST00000543025.5	TSL:1	n.56A>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000438138.1	F5H0A1

Frequencies

GnomAD3 genomes AF: 0.00600 AC: 914 AN: 152242 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00608

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00941

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00532 AC: 1327 AN: 249476 AF XY: 0.00535

Gnomad AFR exome AF: 0.00200

Gnomad AMR exome AF: 0.00409

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00612

Gnomad NFE exome AF: 0.00840

Gnomad OTH exome AF: 0.00611

GnomAD4 exome AF: 0.00737 AC: 10767 AN: 1461780 Hom.: 58 Cov.: 33 AF XY: 0.00712 AC XY: 5175 AN XY: 727206

African (AFR) AF: 0.00191 AC: 64 AN: 33480

American (AMR) AF: 0.00429 AC: 192 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000916 AC: 79 AN: 86244

European-Finnish (FIN) AF: 0.00623 AC: 333 AN: 53416

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00865 AC: 9616 AN: 1111934

Other (OTH) AF: 0.00747 AC: 451 AN: 60392

GnomAD4 genome AF: 0.00600 AC: 914 AN: 152360 Hom.: 2 Cov.: 32 AF XY: 0.00577 AC XY: 430 AN XY: 74514

African (AFR) AF: 0.00255 AC: 106 AN: 41592

American (AMR) AF: 0.00608 AC: 93 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00941 AC: 640 AN: 68034

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00671 Hom.: 8

Bravo AF: 0.00572

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00188 AC: 7

ESP6500EA AF: 0.00673 AC: 55

ExAC AF: 0.00532 AC: 643

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00769

EpiControl AF: 0.00824

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	KDM2B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.67
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.16
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.39
MVP		0.34
MPC		1.3
ClinPred		0.029	T
GERP RS		-0.98
PromoterAI		0.022	Neutral
Varity_R		0.28
gMVP		0.15
Mutation Taster		=96/4	polymorphism

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: rs191586330; hg19: chr12-122018761; COSMIC: COSV65645751; COSMIC: COSV65645751;