Variant rs6464211 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_170606.3(KMT2C):c.8685G>A(p.Gln2895=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,820 control chromosomes in the GnomAD database, including 44,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 12309 hom., cov: 32)

Exomes 𝑓: 0.18 ( 31862 hom. )

Consequence

KMT2C
NM_170606.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.403

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-152176768-C-T is Benign according to our data. Variant chr7-152176768-C-T is described in ClinVar as [Benign]. Clinvar id is 1166982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-152176768-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.403 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2C	NM_170606.3 linkuse as main transcript	c.8685G>A	p.Gln2895=	synonymous_variant	38/59	ENST00000262189.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2C	ENST00000262189.11 linkuse as main transcript	c.8685G>A	p.Gln2895=	synonymous_variant	38/59	1	NM_170606.3	P2	Q8NEZ4-1

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50265

AN:

151946

Hom.:

12273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.242

AC:

60619

AN:

250782

Hom.:

9661

AF XY:

0.231

AC XY:

31356

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.702

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.184

AC:

268976

AN:

1461756

Hom.:

31862

Cov.:

AF XY:

0.185

AC XY:

134771

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.715

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.303

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.331

AC:

50357

AN:

152064

Hom.:

12309

Cov.:

AF XY:

0.333

AC XY:

24787

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.694

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.307

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.199

Hom.:

7342

Bravo

AF:

0.343

Asia WGS

AF:

0.323

AC:

1120

AN:

3478

EpiCase

AF:

0.153

EpiControl

AF:

0.150

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Kleefstra syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.023

DANN

Benign

0.20

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