rs10836123

Positions:

• chr11-33860923-T-G

Variant summary

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

The NM_005574.4(LMO2):​c.465-1348A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,122 control chromosomes in the GnomAD database, including 2,399 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 0.18 (2399 hom., cov: 33)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.465-1348A>C		intron_variant		ENST00000257818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.465-1348A>C		intron_variant		1	NM_005574.4
LMO2	ENST00000395833.7	c.258-1348A>C		intron_variant		1		P1
LMO2	ENST00000411482.1	c.*202-1348A>C		intron_variant, NMD_transcript_variant		1
LMO2	ENST00000464025.5	n.551-1348A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26932 AN: 152004 Hom.: 2397 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.177 AC: 26945 AN: 152122 Hom.: 2399 Cov.: 33 AF XY: 0.177 AC XY: 13188 AN XY: 74360

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.177

Alfa AF: 0.183 Hom.: 1192

Bravo AF: 0.176

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.65

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: rs10836123; hg19: chr11-33882469;