17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACCACCACCACCACCACC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001348716.2(KDM6B):c.768_791dup(p.Pro257_Pro264dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000337 in 1,215,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: KDM6B NM_001348716.2 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6B	NM_001348716.2	c.768_791dup	p.Pro257_Pro264dup	inframe_insertion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.768_791dup	p.Pro257_Pro264dup	inframe_insertion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.768_791dup	p.Pro257_Pro264dup	inframe_insertion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.768_791dup	p.Pro257_Pro264dup	inframe_insertion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+135_711+158dup		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000338 AC: 4 AN: 118294 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000344

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000337 AC: 37 AN: 1097538 Hom.: 0 Cov.: 43 AF XY: 0.0000397 AC XY: 22 AN XY: 554646

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000561

Gnomad4 SAS exome AF: 0.0000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.0000834

GnomAD4 genome AF: 0.0000338 AC: 4 AN: 118294 Hom.: 0 Cov.: 0 AF XY: 0.0000180 AC XY: 1 AN XY: 55440

Gnomad4 AFR AF: 0.0000691

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000344

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61462443; hg19: chr17-7750177;