11-33869356-C-T

Variant names:

• chr11-33869356-C-T
• rs1388899197
• NM_005574.4:c.238G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005574.4(LMO2):​c.238G>A​(p.Asp80Asn) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26010704).

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.238G>A	p.Asp80Asn	missense	Exon 4 of 6	NP_005565.2	P25791-3
	LMO2	NM_001142315.2		c.31G>A	p.Asp11Asn	missense	Exon 2 of 4	NP_001135787.1	P25791-1
	LMO2	NM_001142316.2		c.31G>A	p.Asp11Asn	missense	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.238G>A	p.Asp80Asn	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
	LMO2	ENST00000395833.7	TSL:1	c.31G>A	p.Asp11Asn	missense	Exon 1 of 3	ENSP00000379175.3	P25791-1
	LMO2	ENST00000411482.1	TSL:1	n.31G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151978 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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1059664 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 500360

African (AFR) AF: 0.00 AC: 0 AN: 21558

American (AMR) AF: 0.00 AC: 0 AN: 7210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12770

East Asian (EAS) AF: 0.00 AC: 0 AN: 23880

South Asian (SAS) AF: 0.00 AC: 0 AN: 19230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 898408

Other (OTH) AF: 0.00 AC: 0 AN: 41086

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151978 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74240

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.088
Eigen_PC	Benign	0.068
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N
PhyloP100		5.8
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.10
Sift	Benign	0.065	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.16		Gain of glycosylation at P12 (P = 0.1371)
MVP		0.40
MPC		1.3
ClinPred		0.96	D
GERP RS		4.4
PromoterAI		0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.32
Mutation Taster		=70/30	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: rs1388899197; hg19: chr11-33890902;