rs376781406
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2
The NM_032590.5(KDM2B):c.46C>T(p.Arg16Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,642 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 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
KDM2B
NM_032590.5 stop_gained
NM_032590.5 stop_gained
Scores
1
6
Clinical Significance
Conservation
PhyloP100: -0.126
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 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 4 pathogenic variants in the truncated region.
BS2
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High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM2B | NM_032590.5 | c.46C>T | p.Arg16Ter | stop_gained | 1/23 | ENST00000377071.9 | |
KDM2B-DT | NR_183427.1 | n.356G>A | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM2B | ENST00000377071.9 | c.46C>T | p.Arg16Ter | stop_gained | 1/23 | 1 | NM_032590.5 | P1 | |
KDM2B-DT | ENST00000541574.1 | n.75G>A | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152014Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249334Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135278
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461628Hom.: 0 Cov.: 33 AF XY: 0.0000385 AC XY: 28AN XY: 727134
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GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74240
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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 | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Protein has effects on proliferation and DNA repair. Gene associated with acute myeloid leukemia, pancreatic cancer. Low level of KDM2B found in agressive brain tumors (according to a dissertation from 2008). However, exon 1 is poorly conserved, and there is a framshift variant in this exon in 0.4% of European chromosomes. There really isn't sufficient evidence available to conclude that KDM2B variants cause cancer in humans (no reports of specific variants, just expression studies in tumors and in vitro studies) - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;N
Vest4
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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