17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001348716.2(KDM6B):c.783_791del(p.Pro262_Pro264del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (61 hom., cov: 0)
  • Exomes 𝑓: 0.027 (316 hom.)
  • Failed GnomAD Quality Control
• Consequence: KDM6B NM_001348716.2 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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 Benign. Variant got -8 ACMG points.

• BP6: Variant 17-7846859-TACCACCACC-T is Benign according to our data. Variant chr17-7846859-TACCACCACC-T is described in ClinVar as [Benign]. Clinvar id is 1174808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7846859-TACCACCACC-T is described in Lovd as [Benign]. Variant chr17-7846859-TACCACCACC-T is described in Lovd as [Benign]. Variant chr17-7846859-TACCACCACC-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6B	NM_001348716.2	c.783_791del	p.Pro262_Pro264del	inframe_deletion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.783_791del	p.Pro262_Pro264del	inframe_deletion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.783_791del	p.Pro262_Pro264del	inframe_deletion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.783_791del	p.Pro262_Pro264del	inframe_deletion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+150_711+158del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2768 AN: 118276 Hom.: 61 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00257

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.00215

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.00362

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0265

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0274 AC: 30036 AN: 1094542 Hom.: 316 AF XY: 0.0261 AC XY: 14453 AN XY: 553030

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.000939

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.0383

Gnomad4 NFE exome AF: 0.0318

Gnomad4 OTH exome AF: 0.0244

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0234 AC: 2770 AN: 118338 Hom.: 61 Cov.: 0 AF XY: 0.0234 AC XY: 1300 AN XY: 55494

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.00215

Gnomad4 SAS AF: 0.00250

Gnomad4 FIN AF: 0.0499

Gnomad4 NFE AF: 0.0289

Gnomad4 OTH AF: 0.0262

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

KDM6B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

KDM6B: BS1, BS2 -

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;