11-33864692-C-G

Variant names:

• chr11-33864692-C-G
• rs371147611
• NM_005574.4:c.374G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005574.4(LMO2):​c.374G>C​(p.Ser125Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S125N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO2	NM_005574.4	MANE Select	c.374G>C	p.Ser125Thr	missense	Exon 5 of 6	NP_005565.2	P25791-3
	LMO2	NM_001142315.2		c.167G>C	p.Ser56Thr	missense	Exon 3 of 4	NP_001135787.1	P25791-1
	LMO2	NM_001142316.2		c.167G>C	p.Ser56Thr	missense	Exon 2 of 3	NP_001135788.1	P25791-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO2	ENST00000257818.3	TSL:1 MANE Select	c.374G>C	p.Ser125Thr	missense	Exon 5 of 6	ENSP00000257818.2	P25791-3
	LMO2	ENST00000395833.7	TSL:1	c.167G>C	p.Ser56Thr	missense	Exon 2 of 3	ENSP00000379175.3	P25791-1
	LMO2	ENST00000411482.1	TSL:1	n.*111G>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	0.11	N
PhyloP100		5.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.63
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		0.86	P
Vest4		0.55
MutPred		0.40		Gain of helix (P = 0.132)
MVP		0.84
MPC		1.0
ClinPred		0.55	D
GERP RS		5.4
Varity_R		0.78
gMVP		0.39
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs371147611; hg19: chr11-33886238;