Genetic Variant KMT2E:c.71+20delA (chr7-105041042-TA-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_182931.3(KMT2E):c.71+20delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,089,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

KMT2E
NM_182931.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0350

Publications

0 publications found

Variant links:

Genes affected

KMT2E (HGNC:18541): (lysine methyltransferase 2E (inactive)) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a protein with an N-terminal PHD zinc finger and a central SET domain. Overexpression of the protein inhibits cell cycle progression. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

KMT2E Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
O'Donnell-Luria-Rodan syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KMT2E links:

ENSG00000288914 (HGNC:):

ENSG00000288914 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 7-105041042-TA-T is Benign according to our data. Variant chr7-105041042-TA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2877998.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182931.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KMT2E	NM_182931.3	MANE Select	c.71+20delA	intron	N/A	NP_891847.1	Q8IZD2-1
KMT2E	NM_018682.4		c.71+20delA	intron	N/A	NP_061152.3
KMT2E	NM_001410908.1		c.71+20delA	intron	N/A	NP_001397837.1	Q8IZD2-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KMT2E	ENST00000311117.8	TSL:1 MANE Select	c.71+20delA	intron	N/A	ENSP00000312379.3	Q8IZD2-1
KMT2E	ENST00000473063.2	TSL:1	c.71+20delA	intron	N/A	ENSP00000417156.2	Q8IZD2-7
KMT2E	ENST00000476671.5	TSL:1	c.71+20delA	intron	N/A	ENSP00000417888.1	Q8IZD2-3

Frequencies

GnomAD3 genomes

AF:

0.0000229

AC:

AN:

87264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000699

AC:

AN:

1002104

Hom.:

Cov.:

AF XY:

0.00000196

AC XY:

AN XY:

511012

show subpopulations

African (AFR)

AF:

0.000357

AC:

AN:

19586

American (AMR)

AF:

0.00

AC:

AN:

28646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18718

East Asian (EAS)

AF:

0.00

AC:

AN:

27534

South Asian (SAS)

AF:

0.00

AC:

AN:

67128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

757194

Other (OTH)

AF:

0.00

AC:

AN:

41388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

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:

0.0000229

AC:

AN:

87264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

40546

show subpopulations

African (AFR)

AF:

0.000116

AC:

AN:

17302

American (AMR)

AF:

0.00

AC:

AN:

7376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2588

East Asian (EAS)

AF:

0.00

AC:

AN:

2000

South Asian (SAS)

AF:

0.00

AC:

AN:

2768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

48986

Other (OTH)

AF:

0.00

AC:

AN:

1202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.035

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over