17-7846859-TACCACCACCACCACCACCACCACCACC-TACCACCACCACCACCACC

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BP6_Very_Strong

The NM_001348716.2(KDM6B):c.783_791delACCACCACC(p.Pro262_Pro264del) variant causes a disruptive inframe deletion change. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P261P) has been classified as Likely 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.67

Publications

8 publications found

Variant links:

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]

KDM6B Gene-Disease associations (from GenCC):

syndromic intellectual disability
Inheritance: AD, AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen
neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

KDM6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001348716.2

BP6

Variant 17-7846859-TACCACCACC-T is Benign according to our data. Variant chr17-7846859-TACCACCACC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1174808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6B	NM_001348716.2 link	c.783_791delACCACCACC	p.Pro262_Pro264del	disruptive_inframe_deletion	Exon 10 of 24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2 link	c.783_791delACCACCACC	p.Pro262_Pro264del	disruptive_inframe_deletion	Exon 9 of 22		NP_001073893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KDM6B	ENST00000448097.7 link	c.783_791delACCACCACC	p.Pro262_Pro264del	disruptive_inframe_deletion	Exon 10 of 24	5	NM_001348716.2	ENSP00000412513.2	O15054-2
KDM6B	ENST00000254846.9 link	c.783_791delACCACCACC	p.Pro262_Pro264del	disruptive_inframe_deletion	Exon 9 of 22	1		ENSP00000254846.5	O15054-1
KDM6B	ENST00000570632.1 link	c.711+150_711+158delACCACCACC		intron_variant	Intron 7 of 8	5		ENSP00000458445.1	I3L0Z0

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

2768

AN:

118276

Hom.:

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0154

AC:

395

AN:

25580

American (AMR)

AF:

0.0168

AC:

636

AN:

37766

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

413

AN:

22336

East Asian (EAS)

AF:

0.000939

AC:

AN:

35138

South Asian (SAS)

AF:

0.00206

AC:

154

AN:

74746

European-Finnish (FIN)

AF:

0.0383

AC:

1374

AN:

35884

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

3566

European-Non Finnish (NFE)

AF:

0.0318

AC:

25824

AN:

811632

Other (OTH)

AF:

0.0244

AC:

1169

AN:

47894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.591

Heterozygous variant carriers

1230

2460

3691

4921

6151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

924

1848

2772

3696

4620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0234

AC:

2770

AN:

118338

Hom.:

Cov.:

AF XY:

0.0234

AC XY:

1300

AN XY:

55494

show subpopulations

African (AFR)

AF:

0.0143

AC:

414

AN:

29014

American (AMR)

AF:

0.0214

AC:

250

AN:

11682

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

AN:

3118

East Asian (EAS)

AF:

0.00215

AC:

AN:

4180

South Asian (SAS)

AF:

0.00250

AC:

AN:

3594

European-Finnish (FIN)

AF:

0.0499

AC:

301

AN:

6034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.0289

AC:

1680

AN:

58156

Other (OTH)

AF:

0.0262

AC:

AN:

1528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.594

Heterozygous variant carriers

108

215

323

430

538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0298

Hom.:

2265

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KDM6B: BS1 -

KDM6B-related disorder

Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.7

Mutation Taster

=196/4

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over