11-33869503-C-G

Variant names:

• chr11-33869503-C-G
• rs891057790
• NM_005574.4:c.91G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005574.4(LMO2):​c.91G>C​(p.Asp31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,204,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D31N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14406621).

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.91G>C	p.Asp31His	missense	Exon 4 of 6	NP_005565.2	P25791-3
	LMO2	NM_001142315.2		c.-117G>C		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
	LMO2	NM_001142316.2		c.-117G>C		5_prime_UTR	Exon 1 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.91G>C	p.Asp31His	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
	LMO2	ENST00000395833.7	TSL:1	c.-117G>C		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
	LMO2	ENST00000411482.1	TSL:1	n.-117G>C		non_coding_transcript_exon	Exon 1 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148760 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000189 AC: 2 AN: 1055982 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 506684

African (AFR) AF: 0.00 AC: 0 AN: 20412

American (AMR) AF: 0.00 AC: 0 AN: 6428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11372

East Asian (EAS) AF: 0.00 AC: 0 AN: 20308

South Asian (SAS) AF: 0.00 AC: 0 AN: 23042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2814

European-Non Finnish (NFE) AF: 0.00000222 AC: 2 AN: 899462

Other (OTH) AF: 0.00 AC: 0 AN: 39638

GnomAD4 genome AF: 0.00000672 AC: 1 AN: 148760 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72512

African (AFR) AF: 0.00 AC: 0 AN: 40978

American (AMR) AF: 0.00 AC: 0 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66788

Other (OTH) AF: 0.00 AC: 0 AN: 2040

Alfa AF: 0.0000540 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.94
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.14
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	0.090	N
REVEL	Benign	0.073
Sift	Benign	0.043	D
Sift4G	Benign	0.090	T
Polyphen		0.038	B
Vest4		0.15
MutPred		0.25		Gain of MoRF binding (P = 0.1159)
MVP		0.26
MPC		0.90
ClinPred		0.11	T
GERP RS		2.6
PromoterAI		0.064	Neutral
gMVP		0.29
Mutation Taster		=87/13	polymorphism

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: rs891057790; hg19: chr11-33891049;