rs2038602

Variant names:

• chr11-33864748-A-G
• rs2038602
• NM_005574.4:c.318T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-33864748-A-G
• chr11-33864748-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005574.4(LMO2):​c.318T>C​(p.Ile106Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,613,586 control chromosomes in the GnomAD database, including 140,981 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 0.45 (15685 hom., cov: 32)
  • Exomes 𝑓: 0.41 (125296 hom.)
• Consequence: LMO2 NM_005574.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 23 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.261 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 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.318T>C	p.Ile106Ile	synonymous	Exon 5 of 6	NP_005565.2
	LMO2	NM_001142315.2		c.111T>C	p.Ile37Ile	synonymous	Exon 3 of 4	NP_001135787.1
	LMO2	NM_001142316.2		c.111T>C	p.Ile37Ile	synonymous	Exon 2 of 3	NP_001135788.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO2	ENST00000257818.3	TSL:1 MANE Select	c.318T>C	p.Ile106Ile	synonymous	Exon 5 of 6	ENSP00000257818.2
	LMO2	ENST00000395833.7	TSL:1	c.111T>C	p.Ile37Ile	synonymous	Exon 2 of 3	ENSP00000379175.3
	LMO2	ENST00000411482.1	TSL:1	n.*55T>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000401967.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67559 AN: 151872 Hom.: 15635 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.403

GnomAD2 exomes AF: 0.399 AC: 100039 AN: 250822 AF XY: 0.399

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.387

Gnomad FIN exome AF: 0.530

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.410 AC: 599898 AN: 1461596 Hom.: 125296 Cov.: 52 AF XY: 0.409 AC XY: 297402 AN XY: 727082

African (AFR) AF: 0.558 AC: 18689 AN: 33476

American (AMR) AF: 0.246 AC: 11006 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 8563 AN: 26136

East Asian (EAS) AF: 0.432 AC: 17146 AN: 39698

South Asian (SAS) AF: 0.380 AC: 32738 AN: 86256

European-Finnish (FIN) AF: 0.515 AC: 27398 AN: 53210

Middle Eastern (MID) AF: 0.354 AC: 2044 AN: 5768

European-Non Finnish (NFE) AF: 0.412 AC: 458383 AN: 1111934

Other (OTH) AF: 0.396 AC: 23931 AN: 60396

GnomAD4 genome AF: 0.445 AC: 67665 AN: 151990 Hom.: 15685 Cov.: 32 AF XY: 0.449 AC XY: 33321 AN XY: 74290

African (AFR) AF: 0.552 AC: 22871 AN: 41470

American (AMR) AF: 0.325 AC: 4966 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.409 AC: 2105 AN: 5148

South Asian (SAS) AF: 0.390 AC: 1883 AN: 4832

European-Finnish (FIN) AF: 0.538 AC: 5686 AN: 10566

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27645 AN: 67922

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.409 Hom.: 27914

Bravo AF: 0.435

Asia WGS AF: 0.428 AC: 1489 AN: 3478

EpiCase AF: 0.394

EpiControl AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.8
DANN	Benign	0.67
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2038602; hg19: chr11-33886294; COSMIC: COSV57645575; COSMIC: COSV57645575;