rs3740617

chr11-33859470-T-Achr11-33859470-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005574.4(LMO2):c.570A>T(p.Lys190Asn) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K190K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.570A>T	p.Lys190Asn	missense_variant	6/6	ENST00000257818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.570A>T	p.Lys190Asn	missense_variant	6/6	1	NM_005574.4
LMO2	ENST00000395833.7	c.363A>T	p.Lys121Asn	missense_variant	3/3	1		P1
LMO2	ENST00000464025.5	n.656A>T		non_coding_transcript_exon_variant	2/2	1
LMO2	ENST00000411482.1	c.*307A>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.000022	P;P
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.59
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		1.0	D;D
Vest4		0.71
MutPred		0.51		Loss of methylation at K121 (P = 0.0015);.;
MVP		0.80
MPC		2.0
ClinPred		0.95	D
GERP RS		-0.098
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.74

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

Other links and lift over

dbSNP: rs3740617; hg19: chr11-33881016;