rs1283123920

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-33869466-C-A
• chr11-33869466-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005574.4(LMO2):​c.128G>T​(p.Gly43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,061,714 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. 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. G43E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26457983).

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>T	p.Gly43Val	missense	Exon 4 of 6	NP_005565.2	P25791-3
	LMO2	NM_001142315.2		c.-80G>T		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
	LMO2	NM_001142316.2		c.-80G>T		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>T	p.Gly43Val	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
	LMO2	ENST00000395833.7	TSL:1	c.-80G>T		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
	LMO2	ENST00000411482.1	TSL:1	n.-80G>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000188 AC: 2 AN: 1061714 Hom.: 0 Cov.: 32 AF XY: 0.00000394 AC XY: 2 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: 0.00000221 AC: 2 AN: 904236

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.036
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.079	T
Polyphen		0.18	B
Vest4		0.25
MutPred		0.32		Loss of loop (P = 0.0145)
MVP		0.34
MPC		0.95
ClinPred		0.73	D
GERP RS		1.9
PromoterAI		-0.053	Neutral
gMVP		0.33
Mutation Taster		=67/33	polymorphism

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: rs1283123920; hg19: chr11-33891012;