rs10836127

chr11-33886252-C-A

Variant summary

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

The NM_005574.4(LMO2):c.-335-4365G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,184 control chromosomes in the GnomAD database, including 1,899 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 0.14 (1899 hom., cov: 32)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.-335-4365G>T		intron_variant		ENST00000257818.3
LMO2	XM_017017733.2	c.-264-4365G>T		intron_variant
LMO2	XM_047426944.1	c.-433-3976G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.-335-4365G>T		intron_variant		1	NM_005574.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21693 AN: 152066 Hom.: 1893 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0134

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.143 AC: 21702 AN: 152184 Hom.: 1899 Cov.: 32 AF XY: 0.141 AC XY: 10456 AN XY: 74394

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.148

Alfa AF: 0.176 Hom.: 1601

Bravo AF: 0.141

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.13
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10836127; hg19: chr11-33907798;