17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001348716.2(KDM6B):c.777_791del(p.Pro260_Pro264del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000133 in 1,215,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: KDM6B NM_001348716.2 inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6B	NM_001348716.2	c.777_791del	p.Pro260_Pro264del	inframe_deletion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.777_791del	p.Pro260_Pro264del	inframe_deletion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.777_791del	p.Pro260_Pro264del	inframe_deletion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.777_791del	p.Pro260_Pro264del	inframe_deletion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+144_711+158del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000676 AC: 8 AN: 118286 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000277

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000516

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000140 AC: 154 AN: 1097530 Hom.: 0 AF XY: 0.000121 AC XY: 67 AN XY: 554644

Gnomad4 AFR exome AF: 0.0000391

Gnomad4 AMR exome AF: 0.0000259

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000561

Gnomad4 SAS exome AF: 0.000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.000146

GnomAD4 genome AF: 0.0000676 AC: 8 AN: 118286 Hom.: 0 Cov.: 0 AF XY: 0.0000902 AC XY: 5 AN XY: 55434

Gnomad4 AFR AF: 0.000138

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000277

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000516

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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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;