Variant 12-49051631-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003482.4(KMT2D):c.2052T>A(p.Pro684=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000607 in 1,572,820 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00061 ( 4 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.289

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-49051631-A-T is Benign according to our data. Variant chr12-49051631-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 158748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49051631-A-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.289 with no splicing effect.

BS2

High AC in GnomAd4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2D	NM_003482.4 linkuse as main transcript	c.2052T>A	p.Pro684=	synonymous_variant	11/55	ENST00000301067.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2D	ENST00000301067.12 linkuse as main transcript	c.2052T>A	p.Pro684=	synonymous_variant	11/55	5	NM_003482.4	A2	O14686-1
KMT2D	ENST00000683543.2 linkuse as main transcript	c.2052T>A	p.Pro684=	synonymous_variant	11/56			P4
KMT2D	ENST00000685166.1 linkuse as main transcript	c.2052T>A	p.Pro684=	synonymous_variant	10/54			A2	O14686-3
KMT2D	ENST00000692637.1 linkuse as main transcript	c.2052T>A	p.Pro684=	synonymous_variant	10/54			A2

Frequencies

GnomAD3 genomes

AF:

0.000589

AC:

AN:

149422

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00896

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00403

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.000370

Gnomad OTH

AF:

0.00195

GnomAD3 exomes

AF:

0.000828

AC:

182

AN:

219750

Hom.:

AF XY:

0.000860

AC XY:

101

AN XY:

117400

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.0000932

Gnomad ASJ exome

AF:

0.00867

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00262

Gnomad FIN exome

AF:

0.000104

Gnomad NFE exome

AF:

0.000492

Gnomad OTH exome

AF:

0.000948

GnomAD4 exome

AF:

0.000608

AC:

866

AN:

1423292

Hom.:

Cov.:

AF XY:

0.000693

AC XY:

487

AN XY:

702774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000165

Gnomad4 ASJ exome

AF:

0.00854

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00331

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.000284

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000589

AC:

AN:

149528

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

AN XY:

73028

show subpopulations

Gnomad4 AFR

AF:

0.0000496

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.00896

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00403

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000370

Gnomad4 OTH

AF:

0.00193

Alfa

AF:

0.00165

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	KMT2D: BP4, BP7, BS1 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 26, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 10, 2018

- -

Kabuki syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.3

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over