rs374068805

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003482.4(KMT2D):c.10508-11T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,611,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

KMT2D
NM_003482.4 intron

Scores

Splicing: ADA: 0.02339

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.858

Publications

0 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-49034310-A-C is Benign according to our data. Variant chr12-49034310-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 259053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 66 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003482.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2D	NM_003482.4	MANE Select	c.10508-11T>G		intron	N/A	NP_003473.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KMT2D	ENST00000301067.12	TSL:5 MANE Select	c.10508-11T>G	intron	N/A	ENSP00000301067.7
KMT2D	ENST00000683543.2		c.10508-11T>G	intron	N/A	ENSP00000506726.1
KMT2D	ENST00000685166.1		c.10517-11T>G	intron	N/A	ENSP00000509386.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

248844

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1459188

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

725324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26084

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39626

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000514

AC:

AN:

1109786

Other (OTH)

AF:

0.0000664

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41396

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000662

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Kabuki syndrome

Benign:1

Nov 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Pathogenic

(source)

DANN

Benign

0.65

PhyloP100

0.86

PromoterAI

0.011

Neutral

(source)

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.023

dbscSNV1_RF

Benign

0.27

SpliceAI score (max)

0.62

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.62

Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over