17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001348716.2(KDM6B):c.789_791del(p.Pro264del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (29 hom., cov: 0)
  • Exomes 𝑓: 0.0060 (78 hom.)
  • Failed GnomAD Quality Control
• Consequence: KDM6B NM_001348716.2 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:3
• 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 -2 ACMG points.

• BP6: Variant 17-7846859-TACC-T is Benign according to our data. Variant chr17-7846859-TACC-T is described in ClinVar as [Benign]. Clinvar id is 1300010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7846859-TACC-T is described in Lovd as [Likely_benign]. Variant chr17-7846859-TACC-T is described in Lovd as [Benign]. Variant chr17-7846859-TACC-T is described in Lovd as [Likely_benign]. Variant chr17-7846859-TACC-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6B	NM_001348716.2	c.789_791del	p.Pro264del	inframe_deletion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.789_791del	p.Pro264del	inframe_deletion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.789_791del	p.Pro264del	inframe_deletion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.789_791del	p.Pro264del	inframe_deletion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+156_711+158del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1005 AN: 118290 Hom.: 29 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00806

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00309

Gnomad ASJ AF: 0.0269

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.00116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.00926

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00597 AC: 6547 AN: 1097344 Hom.: 78 AF XY: 0.00580 AC XY: 3215 AN XY: 554574

Gnomad4 AFR exome AF: 0.00664

Gnomad4 AMR exome AF: 0.00246

Gnomad4 ASJ exome AF: 0.0314

Gnomad4 EAS exome AF: 0.0867

Gnomad4 SAS exome AF: 0.00535

Gnomad4 FIN exome AF: 0.000668

Gnomad4 NFE exome AF: 0.00176

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00844 AC: 999 AN: 118352 Hom.: 29 Cov.: 0 AF XY: 0.00976 AC XY: 542 AN XY: 55510

Gnomad4 AFR AF: 0.00803

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.0269

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0103

Gnomad4 FIN AF: 0.00116

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.00916

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

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- -

KDM6B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 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

Likely benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

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- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;