Variant 7-152247986-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 8P and 2B. PVS1BP6_Moderate

The NM_170606.3(KMT2C):c.2447_2448insA(p.Tyr816Ter) variant causes a stop gained, frameshift change. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.49 ( 0 hom., cov: 0)

Exomes 𝑓: 0.49 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KMT2C
NM_170606.3 stop_gained, frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.77

Variant links:

Genes affected

KMT2C (HGNC:13726): (lysine methyltransferase 2C) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a nuclear protein with an AT hook DNA-binding domain, a DHHC-type zinc finger, six PHD-type zinc fingers, a SET domain, a post-SET domain and a RING-type zinc finger. This protein is a member of the ASC-2/NCOA6 complex (ASCOM), which possesses histone methylation activity and is involved in transcriptional coactivation. [provided by RefSeq, Jul 2008]

KMT2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 7-152247986-G-GT is Benign according to our data. Variant chr7-152247986-G-GT is described in ClinVar as [Benign]. Clinvar id is 403020.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2C	NM_170606.3 linkuse as main transcript	c.2447_2448insA	p.Tyr816Ter	stop_gained, frameshift_variant	14/59	ENST00000262189.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2C	ENST00000262189.11 linkuse as main transcript	c.2447_2448insA	p.Tyr816Ter	stop_gained, frameshift_variant	14/59	1	NM_170606.3	P2	Q8NEZ4-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

72119

AN:

145804

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.492

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.492

AC:

635498

AN:

1292742

Hom.:

Cov.:

AF XY:

0.492

AC XY:

317601

AN XY:

645684

show subpopulations

Gnomad4 AFR exome

AF:

0.496

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.489

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.498

Gnomad4 FIN exome

AF:

0.492

Gnomad4 NFE exome

AF:

0.490

Gnomad4 OTH exome

AF:

0.492

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.495

AC:

72179

AN:

145924

Hom.:

Cov.:

AF XY:

0.495

AC XY:

35339

AN XY:

71454

show subpopulations

Gnomad4 AFR

AF:

0.497

Gnomad4 AMR

AF:

0.494

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.498

Gnomad4 FIN

AF:

0.493

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.488

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 25, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: frequency -

Intellectual disability

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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