Genetic Variant LMO2:p.Asp31Asn (chr11-33869503-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005574.4(LMO2):c.91G>A(p.Asp31Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,204,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LMO2
NM_005574.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.145

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1104272).

BS2

High AC in GnomAd4 at 29 AD gene.

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.91G>A	p.Asp31Asn	missense	Exon 4 of 6	NP_005565.2	P25791-3
LMO2	NM_001142315.2		c.-117G>A		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
LMO2	NM_001142316.2		c.-117G>A		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.91G>A	p.Asp31Asn	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
LMO2	ENST00000395833.7	TSL:1	c.-117G>A		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
LMO2	ENST00000411482.1	TSL:1	n.-117G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes

AF:

0.000195

AC:

AN:

148760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000683

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:

0.000490

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1055982

Hom.:

Cov.:

AF XY:

0.00000789

AC XY:

AN XY:

506684

show subpopulations

African (AFR)

AF:

0.000490

AC:

AN:

20412

American (AMR)

AF:

0.00

AC:

AN:

6428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11372

East Asian (EAS)

AF:

0.00

AC:

AN:

20308

South Asian (SAS)

AF:

0.00

AC:

AN:

23042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2814

European-Non Finnish (NFE)

AF:

0.00000111

AC:

AN:

899462

Other (OTH)

AF:

0.0000505

AC:

AN:

39638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000195

AC:

AN:

148760

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

72512

show subpopulations

African (AFR)

AF:

0.000683

AC:

AN:

40978

American (AMR)

AF:

0.00

AC:

AN:

14992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66788

Other (OTH)

AF:

0.000490

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000287

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.30

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

PhyloP100

-0.14

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.070

REVEL

Benign

0.10

Sift

Benign

0.23

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.16

MutPred

0.23

Gain of MoRF binding (P = 0.0958)

MVP

0.33

MPC

0.74

ClinPred

0.17

GERP RS

2.6

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

gMVP

0.17

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over