NM_005574.4:c.128G>A

Variant names:

• chr11-33869466-C-T
• rs1283123920
• NM_005574.4:c.128G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005574.4(LMO2):​c.128G>A​(p.Gly43Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000668 in 149,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26214862).

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.128G>A	p.Gly43Glu	missense	Exon 4 of 6	NP_005565.2	P25791-3
	LMO2	NM_001142315.2		c.-80G>A		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
	LMO2	NM_001142316.2		c.-80G>A		5_prime_UTR	Exon 1 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.128G>A	p.Gly43Glu	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
	LMO2	ENST00000395833.7	TSL:1	c.-80G>A		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
	LMO2	ENST00000411482.1	TSL:1	n.-80G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149702 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1061714 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 507724

African (AFR) AF: 0.00 AC: 0 AN: 20874

American (AMR) AF: 0.00 AC: 0 AN: 6718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11760

East Asian (EAS) AF: 0.00 AC: 0 AN: 21656

South Asian (SAS) AF: 0.00 AC: 0 AN: 21024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 904236

Other (OTH) AF: 0.00 AC: 0 AN: 40334

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149702 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73034

African (AFR) AF: 0.00 AC: 0 AN: 41126

American (AMR) AF: 0.00 AC: 0 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67160

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Uncertain	24
DANN	Benign	0.95
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.1
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.072
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.27	T
Polyphen		0.0060	B
Vest4		0.25
MutPred		0.26		Gain of helix (P = 0.0078)
MVP		0.21
MPC		0.98
ClinPred		0.81	D
GERP RS		1.9
PromoterAI		0.022	Neutral
gMVP		0.23
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs1283123920; hg19: chr11-33891012;