chr17-7846859-TACCACCACCACCACCACC-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001348716.2(KDM6B):c.774_791del(p.Pro259_Pro264del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000126 in 1,215,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
KDM6B
NM_001348716.2 inframe_deletion
NM_001348716.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.67
Genes affected
KDM6B (HGNC:29012): (lysine demethylase 6B) The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM6B | NM_001348716.2 | c.774_791del | p.Pro259_Pro264del | inframe_deletion | 10/24 | ENST00000448097.7 | |
KDM6B | NM_001080424.2 | c.774_791del | p.Pro259_Pro264del | inframe_deletion | 9/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM6B | ENST00000448097.7 | c.774_791del | p.Pro259_Pro264del | inframe_deletion | 10/24 | 5 | NM_001348716.2 | A2 | |
KDM6B | ENST00000254846.9 | c.774_791del | p.Pro259_Pro264del | inframe_deletion | 9/22 | 1 | P2 | ||
KDM6B | ENST00000570632.1 | c.711+141_711+158del | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000127 AC: 15AN: 118292Hom.: 0 Cov.: 0
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GnomAD4 exome AF: 0.000126 AC: 138AN: 1097536Hom.: 0 AF XY: 0.000139 AC XY: 77AN XY: 554648
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KDM6B-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 13, 2022 | The KDM6B c.774_791del18 variant is predicted to result in an in-frame deletion (p.Pro259_Pro264del). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at