17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACC

Variant summary

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

The NM_001348716.2(KDM6B):c.783_791dup(p.Pro262_Pro264dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (469 hom., cov: 0)
  • Exomes 𝑓: 0.067 (1650 hom.)
  • Failed GnomAD Quality Control
• Consequence: KDM6B NM_001348716.2 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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 Benign. Variant got -8 ACMG points.

• BP6: Variant 17-7846859-T-TACCACCACC is Benign according to our data. Variant chr17-7846859-T-TACCACCACC is described in ClinVar as [Benign]. Clinvar id is 1206109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6B	NM_001348716.2	c.783_791dup	p.Pro262_Pro264dup	inframe_insertion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.783_791dup	p.Pro262_Pro264dup	inframe_insertion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.783_791dup	p.Pro262_Pro264dup	inframe_insertion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.783_791dup	p.Pro262_Pro264dup	inframe_insertion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+150_711+158dup		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 9178 AN: 118080 Hom.: 469 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.0900

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0490

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.0726

Gnomad OTH AF: 0.0628

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0667 AC: 72985 AN: 1093504 Hom.: 1650 Cov.: 43 AF XY: 0.0655 AC XY: 36196 AN XY: 552706

Gnomad4 AFR exome AF: 0.0837

Gnomad4 AMR exome AF: 0.0831

Gnomad4 ASJ exome AF: 0.0544

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.0455

Gnomad4 FIN exome AF: 0.0918

Gnomad4 NFE exome AF: 0.0641

Gnomad4 OTH exome AF: 0.0706

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0777 AC: 9182 AN: 118142 Hom.: 469 Cov.: 0 AF XY: 0.0776 AC XY: 4303 AN XY: 55428

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0514

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0958

Gnomad4 NFE AF: 0.0726

Gnomad4 OTH AF: 0.0622

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 17, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified Benign:1

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

Jun 18, 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). -

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;