NM_001348716.2:c.786_791delACCACC

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.786_791delACCACC(p.Pro263_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. P262P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.072 ( 534 hom., cov: 0)

Exomes 𝑓: 0.085 ( 3182 hom. )

Failed GnomAD Quality Control

Consequence

KDM6B
NM_001348716.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

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-TACCACC-T is Benign according to our data. Variant chr17-7846859-TACCACC-T is described in ClinVar as Benign. ClinVar VariationId is 218502.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.786_791delACCACC	p.Pro263_Pro264del	disruptive_inframe_deletion	Exon 10 of 24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2 link	c.786_791delACCACC	p.Pro263_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.786_791delACCACC	p.Pro263_Pro264del	disruptive_inframe_deletion	Exon 10 of 24	5	NM_001348716.2	ENSP00000412513.2	O15054-2
KDM6B	ENST00000254846.9 link	c.786_791delACCACC	p.Pro263_Pro264del	disruptive_inframe_deletion	Exon 9 of 22	1		ENSP00000254846.5	O15054-1
KDM6B	ENST00000570632.1 link	c.711+153_711+158delACCACC		intron_variant	Intron 7 of 8	5		ENSP00000458445.1	I3L0Z0

Frequencies

GnomAD3 genomes

AF:

0.0717

AC:

8477

AN:

118270

Hom.:

531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.0414

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.0764

Gnomad MID

AF:

0.0254

Gnomad NFE

AF:

0.0602

Gnomad OTH

AF:

0.0689

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0847

AC:

92987

AN:

1097262

Hom.:

3182

AF XY:

0.0860

AC XY:

47682

AN XY:

554506

show subpopulations

African (AFR)

AF:

0.0204

AC:

523

AN:

25586

American (AMR)

AF:

0.239

AC:

9237

AN:

38600

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

1023

AN:

22338

East Asian (EAS)

AF:

0.185

AC:

6566

AN:

35538

South Asian (SAS)

AF:

0.172

AC:

13003

AN:

75532

European-Finnish (FIN)

AF:

0.0553

AC:

1988

AN:

35928

Middle Eastern (MID)

AF:

0.0432

AC:

154

AN:

3566

European-Non Finnish (NFE)

AF:

0.0697

AC:

56611

AN:

812230

Other (OTH)

AF:

0.0810

AC:

3882

AN:

47944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

4151

8301

12452

16602

20753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2304

4608

6912

9216

11520

<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:

0.0717

AC:

8487

AN:

118332

Hom.:

534

Cov.:

AF XY:

0.0792

AC XY:

4394

AN XY:

55502

show subpopulations

African (AFR)

AF:

0.0250

AC:

725

AN:

29010

American (AMR)

AF:

0.184

AC:

2153

AN:

11684

Ashkenazi Jewish (ASJ)

AF:

0.0414

AC:

129

AN:

3118

East Asian (EAS)

AF:

0.141

AC:

590

AN:

4178

South Asian (SAS)

AF:

0.217

AC:

781

AN:

3592

European-Finnish (FIN)

AF:

0.0764

AC:

461

AN:

6034

Middle Eastern (MID)

AF:

0.0197

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.0601

AC:

3498

AN:

58158

Other (OTH)

AF:

0.0682

AC:

104

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

310

620

930

1240

1550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0482

Hom.:

2265

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

Significance:Likely benign

Review Status:no assertion criteria provided

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

- -

May 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

May 05, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities

Benign:1

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

European Non-Finnish population allele frequency is 18.48% (rs779500270, 1399/23430 alleles, 15 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.7

Mutation Taster

=200/0

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