rs11168830

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003482.4(KMT2D):c.13689C>T(p.Pro4563Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0573 in 1,613,506 control chromosomes in the GnomAD database, including 5,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 684 hom., cov: 32)

Exomes 𝑓: 0.056 ( 5197 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.30

Publications

16 publications found

Variant links:

Genes affected

KMT2D (HGNC:7133): (lysine methyltransferase 2D) The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

KMT2D Gene-Disease associations (from GenCC):

choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Illumina, G2P
Kabuki syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Kabuki syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KMT2D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 12-49030751-G-A is Benign according to our data. Variant chr12-49030751-G-A is described in ClinVar as Benign. ClinVar VariationId is 94169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4 link	c.13689C>T	p.Pro4563Pro	synonymous_variant	Exon 42 of 55	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12 link	c.13689C>T	p.Pro4563Pro	synonymous_variant	Exon 42 of 55	5	NM_003482.4	ENSP00000301067.7

Frequencies

GnomAD3 genomes

AF:

0.0672

AC:

10225

AN:

152110

Hom.:

679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0525

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.0977

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0664

GnomAD2 exomes

AF:

0.103

AC:

25558

AN:

248488

AF XY:

0.0914

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.0430

Gnomad EAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.0634

Gnomad NFE exome

AF:

0.0361

Gnomad OTH exome

AF:

0.0766

GnomAD4 exome

AF:

0.0562

AC:

82166

AN:

1461278

Hom.:

5197

Cov.:

AF XY:

0.0555

AC XY:

40313

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.0519

AC:

1736

AN:

33474

American (AMR)

AF:

0.307

AC:

13733

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0434

AC:

1135

AN:

26132

East Asian (EAS)

AF:

0.255

AC:

10122

AN:

39700

South Asian (SAS)

AF:

0.0847

AC:

7304

AN:

86256

European-Finnish (FIN)

AF:

0.0631

AC:

3348

AN:

53042

Middle Eastern (MID)

AF:

0.0449

AC:

259

AN:

5768

European-Non Finnish (NFE)

AF:

0.0366

AC:

40668

AN:

1111836

Other (OTH)

AF:

0.0640

AC:

3861

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4102

8204

12305

16407

20509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1928

3856

5784

7712

9640

<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

AF:

0.0673

AC:

10249

AN:

152228

Hom.:

684

Cov.:

AF XY:

0.0706

AC XY:

5253

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0525

AC:

2179

AN:

41544

American (AMR)

AF:

0.188

AC:

2870

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3468

East Asian (EAS)

AF:

0.264

AC:

1362

AN:

5156

South Asian (SAS)

AF:

0.0976

AC:

471

AN:

4826

European-Finnish (FIN)

AF:

0.0607

AC:

644

AN:

10604

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0346

AC:

2354

AN:

68008

Other (OTH)

AF:

0.0733

AC:

155

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

478

957

1435

1914

2392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0469

Hom.:

1130

Bravo

AF:

0.0810

Asia WGS

AF:

0.186

AC:

646

AN:

3478

EpiCase

AF:

0.0340

EpiControl

AF:

0.0347

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -

Feb 23, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kabuki syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.2

(source)

DANN

Benign

0.50

PhyloP100

-1.3

PromoterAI

0.0010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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