Genetic Variant LMO2:n.151G>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 ENST00000464025.5(LMO2):n.151G>A variant causes a non coding transcript exon 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
ENST00000464025.5 non_coding_transcript_exon

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:

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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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4 link	c.249-184G>A		intron_variant	Intron 4 of 5	ENST00000257818.3	NP_005565.2	P25791-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3 link	c.249-184G>A		intron_variant	Intron 4 of 5	1	NM_005574.4	ENSP00000257818.2		P25791-3

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over