11-67231384-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012308.3(KDM2A):​c.1085-182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,046 control chromosomes in the GnomAD database, including 45,968 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 45968 hom., cov: 30)

Consequence

KDM2A
NM_012308.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.167

Publications

7 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDM2ANM_012308.3 linkc.1085-182T>C intron_variant Intron 11 of 20 ENST00000529006.7 NP_036440.1 Q9Y2K7-1I3VM53

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDM2AENST00000529006.7 linkc.1085-182T>C intron_variant Intron 11 of 20 1 NM_012308.3 ENSP00000432786.1 Q9Y2K7-1

Frequencies

GnomAD3 genomes
AF:
0.727
AC:
110376
AN:
151928
Hom.:
45971
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.299
Gnomad AMI
AF:
0.962
Gnomad AMR
AF:
0.689
Gnomad ASJ
AF:
0.946
Gnomad EAS
AF:
0.769
Gnomad SAS
AF:
0.934
Gnomad FIN
AF:
0.891
Gnomad MID
AF:
0.885
Gnomad NFE
AF:
0.934
Gnomad OTH
AF:
0.777
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.726
AC:
110389
AN:
152046
Hom.:
45968
Cov.:
30
AF XY:
0.729
AC XY:
54161
AN XY:
74326
show subpopulations
African (AFR)
AF:
0.299
AC:
12370
AN:
41426
American (AMR)
AF:
0.689
AC:
10521
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.946
AC:
3282
AN:
3470
East Asian (EAS)
AF:
0.769
AC:
3967
AN:
5160
South Asian (SAS)
AF:
0.934
AC:
4503
AN:
4822
European-Finnish (FIN)
AF:
0.891
AC:
9428
AN:
10584
Middle Eastern (MID)
AF:
0.877
AC:
256
AN:
292
European-Non Finnish (NFE)
AF:
0.934
AC:
63546
AN:
68002
Other (OTH)
AF:
0.778
AC:
1641
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
919
1838
2756
3675
4594
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
794
1588
2382
3176
3970
<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:
0.888
Hom.:
29904
Bravo
AF:
0.686
Asia WGS
AF:
0.777
AC:
2703
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
11
DANN
Benign
0.67
PhyloP100
0.17
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs3927807; hg19: chr11-66998855; API