rs10836123

Variant names:

• chr11-33860923-T-G
• rs10836123
• NM_005574.4:c.465-1348A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO2	NM_005574.4	MANE Select	c.465-1348A>C		intron	N/A	NP_005565.2
	LMO2	NM_001142315.2		c.258-1348A>C		intron	N/A	NP_001135787.1
	LMO2	NM_001142316.2		c.258-1348A>C		intron	N/A	NP_001135788.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO2	ENST00000257818.3	TSL:1 MANE Select	c.465-1348A>C		intron	N/A	ENSP00000257818.2
	LMO2	ENST00000395833.7	TSL:1	c.258-1348A>C		intron	N/A	ENSP00000379175.3
	LMO2	ENST00000411482.1	TSL:1	n.*202-1348A>C		intron	N/A	ENSP00000401967.1

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

African (AFR) AF: 0.159 AC: 6580 AN: 41500

American (AMR) AF: 0.156 AC: 2381 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5172

South Asian (SAS) AF: 0.179 AC: 862 AN: 4816

European-Finnish (FIN) AF: 0.174 AC: 1841 AN: 10574

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12781 AN: 67978

Other (OTH) AF: 0.177 AC: 374 AN: 2110

Alfa AF: 0.183 Hom.: 1330

Bravo AF: 0.176

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-0.68
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: rs10836123; hg19: chr11-33882469;