chr17-7846859-TACC-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3BP6_Moderate

The NM_001348716.2(KDM6B):c.789_791delACC(p.Pro264del) variant causes a disruptive inframe deletion change. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P263P) has been classified as Likely 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:4

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: Likely_benign. The variant received -3 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001348716.2

BP6

Variant 17-7846859-TACC-T is Benign according to our data. Variant chr17-7846859-TACC-T is described in ClinVar as Benign. ClinVar VariationId is 1300010.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6B	NM_001348716.2 link	c.789_791delACC	p.Pro264del	disruptive_inframe_deletion	Exon 10 of 24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2 link	c.789_791delACC	p.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.789_791delACC	p.Pro264del	disruptive_inframe_deletion	Exon 10 of 24	5	NM_001348716.2	ENSP00000412513.2	O15054-2
KDM6B	ENST00000254846.9 link	c.789_791delACC	p.Pro264del	disruptive_inframe_deletion	Exon 9 of 22	1		ENSP00000254846.5	O15054-1
KDM6B	ENST00000570632.1 link	c.711+156_711+158delACC		intron_variant	Intron 7 of 8	5		ENSP00000458445.1	I3L0Z0

Frequencies

GnomAD3 genomes

AF:

0.00850

AC:

1005

AN:

118290

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00580

AC XY:

3215

AN XY:

554574

show subpopulations

African (AFR)

AF:

0.00664

AC:

170

AN:

25584

American (AMR)

AF:

0.00246

AC:

AN:

38604

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

702

AN:

22350

East Asian (EAS)

AF:

0.0867

AC:

3087

AN:

35624

South Asian (SAS)

AF:

0.00535

AC:

404

AN:

75536

European-Finnish (FIN)

AF:

0.000668

AC:

AN:

35928

Middle Eastern (MID)

AF:

0.00393

AC:

AN:

3566

European-Non Finnish (NFE)

AF:

0.00176

AC:

1433

AN:

812198

Other (OTH)

AF:

0.0129

AC:

618

AN:

47954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

302

603

905

1206

1508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.00844

AC:

999

AN:

118352

Hom.:

Cov.:

AF XY:

0.00976

AC XY:

542

AN XY:

55510

show subpopulations

African (AFR)

AF:

0.00803

AC:

233

AN:

29016

American (AMR)

AF:

0.00308

AC:

AN:

11684

Ashkenazi Jewish (ASJ)

AF:

0.0269

AC:

AN:

3118

East Asian (EAS)

AF:

0.117

AC:

490

AN:

4176

South Asian (SAS)

AF:

0.0103

AC:

AN:

3594

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

6038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00168

AC:

AN:

58166

Other (OTH)

AF:

0.00916

AC:

AN:

1528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00831

Hom.:

2265

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

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

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

- -

KDM6B-related disorder

Benign:1

Oct 31, 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). -

not provided

Benign:1

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.7

Mutation Taster

=77/23

polymorphism

(source)

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

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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