NM_001348716.2:c.786_791dupACCACC

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_791dupACCACC(p.Pro263_Pro264dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 34367 hom., cov: 0)

Exomes 𝑓: 0.56 ( 124679 hom. )

Failed GnomAD Quality Control

Consequence

KDM6B
NM_001348716.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:4

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-TACCACC is Benign according to our data. Variant chr17-7846859-T-TACCACC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254122.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_791dupACCACC	p.Pro263_Pro264dup	disruptive_inframe_insertion	Exon 10 of 24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2 link	c.786_791dupACCACC	p.Pro263_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.786_791dupACCACC	p.Pro263_Pro264dup	disruptive_inframe_insertion	Exon 10 of 24	5	NM_001348716.2	ENSP00000412513.2	O15054-2
KDM6B	ENST00000254846.9 link	c.786_791dupACCACC	p.Pro263_Pro264dup	disruptive_inframe_insertion	Exon 9 of 22	1		ENSP00000254846.5	O15054-1
KDM6B	ENST00000570632.1 link	c.711+153_711+158dupACCACC		intron_variant	Intron 7 of 8	5		ENSP00000458445.1	I3L0Z0

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

89411

AN:

117718

Hom.:

34351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.830

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.801

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.722

Gnomad MID

AF:

0.895

Gnomad NFE

AF:

0.795

Gnomad OTH

AF:

0.771

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.565

AC:

614608

AN:

1088244

Hom.:

124679

Cov.:

AF XY:

0.559

AC XY:

307306

AN XY:

549990

show subpopulations

African (AFR)

AF:

0.549

AC:

13952

AN:

25402

American (AMR)

AF:

0.420

AC:

16106

AN:

38302

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

12099

AN:

22238

East Asian (EAS)

AF:

0.415

AC:

14583

AN:

35160

South Asian (SAS)

AF:

0.493

AC:

36985

AN:

75064

European-Finnish (FIN)

AF:

0.467

AC:

16679

AN:

35690

Middle Eastern (MID)

AF:

0.576

AC:

2038

AN:

3540

European-Non Finnish (NFE)

AF:

0.591

AC:

476131

AN:

805258

Other (OTH)

AF:

0.547

AC:

26035

AN:

47590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.599

Heterozygous variant carriers

11436

22873

34309

45746

57182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12804

25608

38412

51216

64020

<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:

0.760

AC:

89456

AN:

117782

Hom.:

34367

Cov.:

AF XY:

0.750

AC XY:

41431

AN XY:

55212

show subpopulations

African (AFR)

AF:

0.758

AC:

21911

AN:

28910

American (AMR)

AF:

0.676

AC:

7810

AN:

11548

Ashkenazi Jewish (ASJ)

AF:

0.801

AC:

2492

AN:

3110

East Asian (EAS)

AF:

0.574

AC:

2388

AN:

4158

South Asian (SAS)

AF:

0.668

AC:

2382

AN:

3566

European-Finnish (FIN)

AF:

0.722

AC:

4331

AN:

5998

Middle Eastern (MID)

AF:

0.906

AC:

230

AN:

254

European-Non Finnish (NFE)

AF:

0.796

AC:

46087

AN:

57934

Other (OTH)

AF:

0.773

AC:

1179

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

774

1547

2321

3094

3868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.626

Hom.:

2265

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities

Benign:2

Jan 18, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 77.92% (rs779500270, 8811/11110 alleles, 3564 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.4.0, this variant is classified as BENIGN. Following criteria are met: BA1 -

Oromandibular-limb hypogenesis spectrum

Uncertain:1

Aug 12, 2016

CHU Sainte-Justine Research Center, University of Montreal

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

not specified

Benign:1

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

Feb 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 33337535) -

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