Genetic Variant LMO2:p.Lys190Lys (chr11-33859470-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005574.4(LMO2):c.570A>G(p.Lys190Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,613,584 control chromosomes in the GnomAD database, including 295,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.58 ( 26014 hom., cov: 31)

Exomes 𝑓: 0.60 ( 269044 hom. )

Consequence

LMO2
NM_005574.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-33859470-T-C is Benign according to our data. Variant chr11-33859470-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.397 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4 link	c.570A>G	p.Lys190Lys	synonymous_variant	Exon 6 of 6	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.570A>G	p.Lys190Lys	synonymous_variant	Exon 6 of 6	1	NM_005574.4	ENSP00000257818.2		P25791-3

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88079

AN:

151832

Hom.:

26004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.628

GnomAD3 exomes

AF:

0.610

AC:

153439

AN:

251388

Hom.:

47807

AF XY:

0.610

AC XY:

82877

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.771

Gnomad ASJ exome

AF:

0.676

Gnomad EAS exome

AF:

0.519

Gnomad SAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.482

Gnomad NFE exome

AF:

0.605

Gnomad OTH exome

AF:

0.634

GnomAD4 exome

AF:

0.604

AC:

882866

AN:

1461634

Hom.:

269044

Cov.:

AF XY:

0.605

AC XY:

440025

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.503

Gnomad4 AMR exome

AF:

0.764

Gnomad4 ASJ exome

AF:

0.677

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.628

Gnomad4 FIN exome

AF:

0.496

Gnomad4 NFE exome

AF:

0.607

Gnomad4 OTH exome

AF:

0.613

GnomAD4 genome

AF:

0.580

AC:

88103

AN:

151950

Hom.:

26014

Cov.:

AF XY:

0.575

AC XY:

42688

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.507

Gnomad4 AMR

AF:

0.695

Gnomad4 ASJ

AF:

0.685

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.620

Alfa

AF:

0.612

Hom.:

58916

Bravo

AF:

0.591

Asia WGS

AF:

0.530

AC:

1844

AN:

3478

EpiCase

AF:

0.623

EpiControl

AF:

0.620

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.3

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over