Genetic Variant LMO2:p.Gly35Ser (chr11-33869491-C-T) – 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.103G>A(p.Gly35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G35C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMO2
NM_005574.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.105

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=0.27277112).

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.103G>A	p.Gly35Ser	missense	Exon 4 of 6	NP_005565.2	P25791-3
LMO2	NM_001142315.2		c.-105G>A		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
LMO2	NM_001142316.2		c.-105G>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.103G>A	p.Gly35Ser	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
LMO2	ENST00000395833.7	TSL:1	c.-105G>A		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
LMO2	ENST00000411482.1	TSL:1	n.-105G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1054844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

505198

African (AFR)

AF:

0.00

AC:

AN:

20494

American (AMR)

AF:

0.00

AC:

AN:

6444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11330

East Asian (EAS)

AF:

0.00

AC:

AN:

20528

South Asian (SAS)

AF:

0.00

AC:

AN:

21898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

899408

Other (OTH)

AF:

0.00

AC:

AN:

39668

GnomAD4 genome

Cov.:

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

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.93

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.33

M_CAP

Benign

0.073

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.85

PhyloP100

0.10

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.050

REVEL

Benign

0.088

Sift

Pathogenic

0.0

Sift4G

Benign

0.48

Polyphen

1.0

Vest4

0.18

MutPred

0.31

Gain of glycosylation at G35 (P = 0.002)

MVP

0.43

MPC

0.76

ClinPred

0.61

GERP RS

1.3

PromoterAI

-0.031

Neutral

(source)

gMVP

0.20

Mutation Taster

=91/9

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over