chr7-105041005-A-G

Variant names:

• chr7-105041005-A-G
• NM_182931.3:c.53A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182931.3(KMT2E):​c.53A>G​(p.Glu18Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KMT2E NM_182931.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.29

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]

ENSG00000288914 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2E	NM_182931.3	c.53A>G	p.Glu18Gly	missense_variant	Exon 3 of 27	ENST00000311117.8	NP_891847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2E	ENST00000311117.8	c.53A>G	p.Glu18Gly	missense_variant	Exon 3 of 27	1	NM_182931.3	ENSP00000312379.3
ENSG00000288914	ENST00000688005.1	c.*49A>G		downstream_gene_variant				ENSP00000510606.1
ENSG00000289360	ENST00000685210.1	c.*80A>G		downstream_gene_variant				ENSP00000510327.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 13, 2019

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.;T;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	.;D;D;D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	0.0	N;N;.;.;N;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.0	D;D;N;D;D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D;D;T;D;D;D
Sift4G	Uncertain	0.0050	D;D;T;D;D;D
Polyphen		0.49	P;P;.;.;P;.
Vest4		0.54
MutPred		0.34		Loss of stability (P = 0.0426);Loss of stability (P = 0.0426);Loss of stability (P = 0.0426);Loss of stability (P = 0.0426);Loss of stability (P = 0.0426);Loss of stability (P = 0.0426);
MVP		0.89
MPC		0.65
ClinPred		0.94	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-104681452;