11-33865001-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005574.4(LMO2):c.249-184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 646,588 control chromosomes in the GnomAD database, including 44,459 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 0.34 (9152 hom., cov: 32)
  • Exomes 𝑓: 0.37 (35307 hom.)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.249-184G>A		intron_variant		ENST00000257818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.249-184G>A		intron_variant		1	NM_005574.4

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51374 AN: 151876 Hom.: 9143 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.367 AC: 181538 AN: 494594 Hom.: 35307 Cov.: 4 AF XY: 0.372 AC XY: 97450 AN XY: 261986

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.469

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.338 AC: 51385 AN: 151994 Hom.: 9152 Cov.: 32 AF XY: 0.343 AC XY: 25489 AN XY: 74280

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.359

Alfa AF: 0.314 Hom.: 4145

Bravo AF: 0.351

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.68
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs3824848; hg19: chr11-33886547;