Genetic Variant LMO2:c.249-184G>A (chr11-33865001-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005574.4(LMO2):c.249-184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 646,588 control chromosomes in the GnomAD database, including 44,459 homozygotes. 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: 𝑓 0.34 ( 9152 hom., cov: 32)

Exomes 𝑓: 0.37 ( 35307 hom. )

Consequence

LMO2
NM_005574.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.24

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

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	Effect	Exon Rank	Protein
LMO2	NM_005574.4	MANE Select	c.249-184G>A	intron	N/A	NP_005565.2
LMO2	NM_001142315.2		c.42-184G>A	intron	N/A	NP_001135787.1
LMO2	NM_001142316.2		c.42-184G>A	intron	N/A	NP_001135788.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LMO2	ENST00000257818.3	TSL:1 MANE Select	c.249-184G>A	intron	N/A	ENSP00000257818.2
LMO2	ENST00000395833.7	TSL:1	c.42-184G>A	intron	N/A	ENSP00000379175.3
LMO2	ENST00000464025.5	TSL:1	n.151G>A	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51374

AN:

151876

Hom.:

9143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.363

GnomAD4 exome

AF:

0.367

AC:

181538

AN:

494594

Hom.:

35307

Cov.:

AF XY:

0.372

AC XY:

97450

AN XY:

261986

show subpopulations

African (AFR)

AF:

0.285

AC:

4166

AN:

14630

American (AMR)

AF:

0.602

AC:

18254

AN:

30332

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

5564

AN:

15982

East Asian (EAS)

AF:

0.473

AC:

14830

AN:

31324

South Asian (SAS)

AF:

0.469

AC:

24550

AN:

52348

European-Finnish (FIN)

AF:

0.292

AC:

8864

AN:

30368

Middle Eastern (MID)

AF:

0.322

AC:

1218

AN:

3780

European-Non Finnish (NFE)

AF:

0.326

AC:

93768

AN:

287730

Other (OTH)

AF:

0.367

AC:

10324

AN:

28100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

6068

12137

18205

24274

30342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.338

AC:

51385

AN:

151994

Hom.:

9152

Cov.:

AF XY:

0.343

AC XY:

25489

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.286

AC:

11842

AN:

41464

American (AMR)

AF:

0.479

AC:

7305

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1232

AN:

3470

East Asian (EAS)

AF:

0.506

AC:

2610

AN:

5156

South Asian (SAS)

AF:

0.469

AC:

2255

AN:

4810

European-Finnish (FIN)

AF:

0.281

AC:

2976

AN:

10584

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21958

AN:

67932

Other (OTH)

AF:

0.359

AC:

757

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1708

3416

5124

6832

8540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.315

Hom.:

4619

Bravo

AF:

0.351

Asia WGS

AF:

0.462

AC:

1606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.68

(source)

DANN

Benign

0.67

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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