Genetic Variant LMO2:p.Gly43Val (chr11-33869466-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005574.4(LMO2):c.128G>T(p.Gly43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,061,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G43E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

LMO2
NM_005574.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26457983).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005574.4. 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.128G>T	p.Gly43Val	missense	Exon 4 of 6	NP_005565.2	P25791-3
LMO2	NM_001142315.2		c.-80G>T		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
LMO2	NM_001142316.2		c.-80G>T		5_prime_UTR	Exon 1 of 3	NP_001135788.1	P25791-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMO2	ENST00000257818.3	TSL:1 MANE Select	c.128G>T	p.Gly43Val	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
LMO2	ENST00000395833.7	TSL:1	c.-80G>T		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
LMO2	ENST00000411482.1	TSL:1	n.-80G>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000188

AC:

AN:

1061714

Hom.:

Cov.:

AF XY:

0.00000394

AC XY:

AN XY:

507724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20874

American (AMR)

AF:

0.00

AC:

AN:

6718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11760

East Asian (EAS)

AF:

0.00

AC:

AN:

21656

South Asian (SAS)

AF:

0.00

AC:

AN:

21024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2680

European-Non Finnish (NFE)

AF:

0.00000221

AC:

AN:

904236

Other (OTH)

AF:

0.00

AC:

AN:

40334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

PhyloP100

2.1

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.3

REVEL

Benign

0.036

Sift

Uncertain

0.0040

Sift4G

Benign

0.079

Polyphen

0.18

Vest4

0.25

MutPred

0.32

Loss of loop (P = 0.0145)

MVP

0.34

MPC

0.95

ClinPred

0.73

GERP RS

1.9

PromoterAI

-0.053

Neutral

(source)

gMVP

0.33

Mutation Taster

=67/33

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