11-33859550-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005574.4(LMO2):c.490G>T(p.Ala164Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.490G>T	p.Ala164Ser	missense_variant	6/6	ENST00000257818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.490G>T	p.Ala164Ser	missense_variant	6/6	1	NM_005574.4
LMO2	ENST00000395833.7	c.283G>T	p.Ala95Ser	missense_variant	3/3	1		P1
LMO2	ENST00000464025.5	n.576G>T		non_coding_transcript_exon_variant	2/2	1
LMO2	ENST00000411482.1	c.*227G>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.490G>T (p.A164S) alteration is located in exon 6 (coding exon 4) of the LMO2 gene. This alteration results from a G to T substitution at nucleotide position 490, causing the alanine (A) at amino acid position 164 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
Cadd	Benign	23
Dann	Benign	0.85
DEOGEN2	Uncertain	0.56	D;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	0.30	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.53
Sift	Benign	0.41	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.99	D;P
Vest4		0.64
MutPred		0.61		Loss of sheet (P = 0.0457);.;
MVP		0.74
MPC		0.72
ClinPred		0.52	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-33881096;