chr17-7846859-T-TACCACCACC

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_791dupACCACCACC(p.Pro262_Pro264dup) variant causes a disruptive 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 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.250

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-T-TACCACCACC is Benign according to our data. Variant chr17-7846859-T-TACCACCACC is described in ClinVar as Benign. ClinVar VariationId is 1206109.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_791dupACCACCACC	p.Pro262_Pro264dup	disruptive_inframe_insertion	Exon 10 of 24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2 link	c.783_791dupACCACCACC	p.Pro262_Pro264dup	disruptive_inframe_insertion	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_791dupACCACCACC	p.Pro262_Pro264dup	disruptive_inframe_insertion	Exon 10 of 24	5	NM_001348716.2	ENSP00000412513.2	O15054-2
KDM6B	ENST00000254846.9 link	c.783_791dupACCACCACC	p.Pro262_Pro264dup	disruptive_inframe_insertion	Exon 9 of 22	1		ENSP00000254846.5	O15054-1
KDM6B	ENST00000570632.1 link	c.711+150_711+158dupACCACCACC		intron_variant	Intron 7 of 8	5		ENSP00000458445.1	I3L0Z0

Frequencies

GnomAD3 genomes

AF:

0.0777

AC:

9178

AN:

118080

Hom.:

469

Cov.:

show subpopulations

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.:

AF XY:

0.0655

AC XY:

36196

AN XY:

552706

show subpopulations

African (AFR)

AF:

0.0837

AC:

2134

AN:

25500

American (AMR)

AF:

0.0831

AC:

3206

AN:

38582

Ashkenazi Jewish (ASJ)

AF:

0.0544

AC:

1214

AN:

22320

East Asian (EAS)

AF:

0.123

AC:

4362

AN:

35572

South Asian (SAS)

AF:

0.0455

AC:

3434

AN:

75434

European-Finnish (FIN)

AF:

0.0918

AC:

3296

AN:

35910

Middle Eastern (MID)

AF:

0.0413

AC:

147

AN:

3556

European-Non Finnish (NFE)

AF:

0.0641

AC:

51816

AN:

808796

Other (OTH)

AF:

0.0706

AC:

3376

AN:

47834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

3160

6320

9480

12640

15800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1674

3348

5022

6696

8370

<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:

0.0777

AC:

9182

AN:

118142

Hom.:

469

Cov.:

AF XY:

0.0776

AC XY:

4303

AN XY:

55428

show subpopulations

African (AFR)

AF:

0.0865

AC:

2507

AN:

28976

American (AMR)

AF:

0.0716

AC:

834

AN:

11640

Ashkenazi Jewish (ASJ)

AF:

0.0514

AC:

160

AN:

3112

East Asian (EAS)

AF:

0.130

AC:

541

AN:

4176

South Asian (SAS)

AF:

0.0487

AC:

175

AN:

3592

European-Finnish (FIN)

AF:

0.0958

AC:

577

AN:

6024

Middle Eastern (MID)

AF:

0.0394

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.0726

AC:

4213

AN:

58062

Other (OTH)

AF:

0.0622

AC:

AN:

1528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

343

687

1030

1374

1717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0690

Hom.:

2265

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

KDM6B-related disorder

Benign:1

Jun 18, 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

0.25

Mutation Taster

=89/11

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