11-67250140-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012308.3(KDM2A):āc.2110C>Gā(p.Pro704Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,076 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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
KDM2A
NM_012308.3 missense
NM_012308.3 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 5.63
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18808651).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KDM2A | NM_012308.3 | c.2110C>G | p.Pro704Ala | missense_variant | 17/21 | ENST00000529006.7 | NP_036440.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KDM2A | ENST00000529006.7 | c.2110C>G | p.Pro704Ala | missense_variant | 17/21 | 1 | NM_012308.3 | ENSP00000432786.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246860Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134012
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460076Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726236
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2024 | The c.2110C>G (p.P704A) alteration is located in exon 17 (coding exon 16) of the KDM2A gene. This alteration results from a C to G substitution at nucleotide position 2110, causing the proline (P) at amino acid position 704 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.;N
REVEL
Benign
Sift
Uncertain
D;D;.;T
Sift4G
Benign
T;T;T;T
Polyphen
0.017
.;B;.;.
Vest4
MutPred
Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);.;.;
MVP
MPC
0.84
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at