11-33882268-C-T

Variant names:

• chr11-33882268-C-T
• rs1885523
• NM_005574.4:c.-335-381G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005574.4(LMO2):​c.-335-381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,028 control chromosomes in the GnomAD database, including 16,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16504 hom., cov: 32)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

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.-335-381G>A		intron	N/A	NP_005565.2	P25791-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO2	ENST00000257818.3	TSL:1 MANE Select	c.-335-381G>A		intron	N/A	ENSP00000257818.2	P25791-3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70115 AN: 151910 Hom.: 16470 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.462 AC: 70196 AN: 152028 Hom.: 16504 Cov.: 32 AF XY: 0.463 AC XY: 34396 AN XY: 74320

African (AFR) AF: 0.381 AC: 15779 AN: 41432

American (AMR) AF: 0.469 AC: 7174 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2106 AN: 5178

South Asian (SAS) AF: 0.491 AC: 2367 AN: 4816

European-Finnish (FIN) AF: 0.521 AC: 5500 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34198 AN: 67978

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.488 Hom.: 69354

Bravo AF: 0.455

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.48
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1885523; hg19: chr11-33903814;