11-33859470-T-C

Variant names:

• chr11-33859470-T-C
• rs3740617
• NM_005574.4:c.570A>G

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.570A>G​(p.Lys190Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,613,584 control chromosomes in the GnomAD database, including 295,058 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 0.58 (26014 hom., cov: 31)
  • Exomes 𝑓: 0.60 (269044 hom.)
• Consequence: LMO2 NM_005574.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 32 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=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.397 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 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.570A>G	p.Lys190Lys	synonymous	Exon 6 of 6	NP_005565.2	P25791-3
	LMO2	NM_001142315.2		c.363A>G	p.Lys121Lys	synonymous	Exon 4 of 4	NP_001135787.1	P25791-1
	LMO2	NM_001142316.2		c.363A>G	p.Lys121Lys	synonymous	Exon 3 of 3	NP_001135788.1	P25791-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO2	ENST00000257818.3	TSL:1 MANE Select	c.570A>G	p.Lys190Lys	synonymous	Exon 6 of 6	ENSP00000257818.2	P25791-3
	LMO2	ENST00000395833.7	TSL:1	c.363A>G	p.Lys121Lys	synonymous	Exon 3 of 3	ENSP00000379175.3	P25791-1
	LMO2	ENST00000411482.1	TSL:1	n.*307A>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88079 AN: 151832 Hom.: 26004 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.628

GnomAD2 exomes AF: 0.610 AC: 153439 AN: 251388 AF XY: 0.610

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.676

Gnomad EAS exome AF: 0.519

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.605

Gnomad OTH exome AF: 0.634

GnomAD4 exome AF: 0.604 AC: 882866 AN: 1461634 Hom.: 269044 Cov.: 45 AF XY: 0.605 AC XY: 440025 AN XY: 727146

African (AFR) AF: 0.503 AC: 16835 AN: 33472

American (AMR) AF: 0.764 AC: 34163 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 17688 AN: 26134

East Asian (EAS) AF: 0.456 AC: 18103 AN: 39700

South Asian (SAS) AF: 0.628 AC: 54157 AN: 86254

European-Finnish (FIN) AF: 0.496 AC: 26471 AN: 53418

Middle Eastern (MID) AF: 0.660 AC: 3808 AN: 5768

European-Non Finnish (NFE) AF: 0.607 AC: 674598 AN: 1111778

Other (OTH) AF: 0.613 AC: 37043 AN: 60386

GnomAD4 genome AF: 0.580 AC: 88103 AN: 151950 Hom.: 26014 Cov.: 31 AF XY: 0.575 AC XY: 42688 AN XY: 74222

African (AFR) AF: 0.507 AC: 21013 AN: 41428

American (AMR) AF: 0.695 AC: 10610 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2380 AN: 3472

East Asian (EAS) AF: 0.498 AC: 2565 AN: 5150

South Asian (SAS) AF: 0.615 AC: 2967 AN: 4824

European-Finnish (FIN) AF: 0.473 AC: 4985 AN: 10540

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.612 AC: 41583 AN: 67950

Other (OTH) AF: 0.620 AC: 1306 AN: 2108

Alfa AF: 0.604 Hom.: 121633

Bravo AF: 0.591

Asia WGS AF: 0.530 AC: 1844 AN: 3478

EpiCase AF: 0.623

EpiControl AF: 0.620

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.3
DANN	Benign	0.53
PhyloP100		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs3740617; hg19: chr11-33881016; COSMIC: COSV57645265;