Genetic Variant LMO2:c.-158C>T (chr11-33869544-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142315.2(LMO2):c.-158C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000889 in 1,124,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

LMO2
NM_001142315.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

Genes affected

LMO2 (HGNC:6642): (LIM domain only 2) LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Nov 2008]

LMO2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17836651).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142315.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMO2	NM_005574.4	MANE Select	c.50C>T	p.Pro17Leu	missense	Exon 4 of 6	NP_005565.2	P25791-3
LMO2	NM_001142315.2		c.-158C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_001135787.1	P25791-1
LMO2	NM_001142316.2		c.-158C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001135788.1	P25791-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMO2	ENST00000395833.7	TSL:1	c.-158C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000379175.3	P25791-1
LMO2	ENST00000257818.3	TSL:1 MANE Select	c.50C>T	p.Pro17Leu	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
LMO2	ENST00000395833.7	TSL:1	c.-158C>T		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.89e-7

AC:

AN:

1124926

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

548996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21294

American (AMR)

AF:

0.00

AC:

AN:

11516

Ashkenazi Jewish (ASJ)

AF:

0.0000642

AC:

AN:

15570

East Asian (EAS)

AF:

0.00

AC:

AN:

21406

South Asian (SAS)

AF:

0.00

AC:

AN:

41302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3672

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

931402

Other (OTH)

AF:

0.00

AC:

AN:

42336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.93

PhyloP100

1.1

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.3

REVEL

Benign

0.055

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.058

Polyphen

0.0030

Vest4

0.067

MutPred

0.29

Loss of glycosylation at P17 (P = 0.0203)

MVP

0.12

MPC

0.78

ClinPred

0.62

GERP RS

2.8

PromoterAI

0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

gMVP

0.47

Mutation Taster

=91/9

polymorphism

(source)

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