dbSNP rs201937858: KDM2A:p.Arg347His (chr11-67228119-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012308.3(KDM2A):c.1040G>A(p.Arg347His) variant causes a missense change. The variant allele was found at a frequency of 0.000175 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KDM2A
NM_012308.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Publications

3 publications found

Variant links:

Genes affected

KDM2A (HGNC:13606): (lysine demethylase 2A) 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 and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

KDM2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.057006925).

BS2

High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012308.3. 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
	KDM2A	NM_012308.3	MANE Select	c.1040G>A	p.Arg347His	missense	Exon 11 of 21	NP_036440.1	Q9Y2K7-1
	KDM2A	NR_027473.2		n.1910G>A		non_coding_transcript_exon	Exon 11 of 21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM2A	ENST00000529006.7	TSL:1 MANE Select	c.1040G>A	p.Arg347His	missense	Exon 11 of 21	ENSP00000432786.1	Q9Y2K7-1
KDM2A	ENST00000308783.9	TSL:1	c.989G>A	p.Arg330His	missense	Exon 11 of 21	ENSP00000309302.6	I3VM54
KDM2A	ENST00000398645.6	TSL:1	c.1040G>A	p.Arg347His	missense	Exon 11 of 21	ENSP00000381640.2	Q9Y2K7-3

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000233

AC:

AN:

249264

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000301

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

253

AN:

1461376

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

127

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33476

American (AMR)

AF:

0.000760

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000188

AC:

209

AN:

1111564

Other (OTH)

AF:

0.000116

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41514

American (AMR)

AF:

0.000785

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000291

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000207

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0067

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

4.0

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.40

Polyphen

0.92

Vest4

0.14

MutPred

0.45

Gain of helix (P = 0.062)

MVP

0.38

MPC

1.0

ClinPred

0.066

GERP RS

6.0

Varity_R

0.31

gMVP

0.64

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over