NM_005574.4:c.50C>A

Variant names:

• chr11-33869544-G-T
• rs995264473
• NM_005574.4:c.50C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005574.4(LMO2):​c.50C>A​(p.Pro17Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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. P17R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMO2 NM_005574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28029305).

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.50C>A	p.Pro17Gln	missense	Exon 4 of 6	NP_005565.2	P25791-3
	LMO2	NM_001142315.2		c.-158C>A		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
	LMO2	NM_001142316.2		c.-158C>A		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.50C>A	p.Pro17Gln	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
	LMO2	ENST00000395833.7	TSL:1	c.-158C>A		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
	LMO2	ENST00000969327.1		c.50C>A	p.Pro17Gln	missense	Exon 3 of 5	ENSP00000639386.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1124926 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 548996

African (AFR) AF: 0.00 AC: 0 AN: 21294

American (AMR) AF: 0.00 AC: 0 AN: 11516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15570

East Asian (EAS) AF: 0.00 AC: 0 AN: 21406

South Asian (SAS) AF: 0.00 AC: 0 AN: 41302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 931402

Other (OTH) AF: 0.00 AC: 0 AN: 42336

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Benign	0.97
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.92	T
PhyloP100		1.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.015	D
Polyphen		0.89	P
Vest4		0.13
MutPred		0.31		Loss of glycosylation at P17 (P = 0.0203)
MVP		0.16
MPC		0.70
ClinPred		0.54	D
GERP RS		2.8
PromoterAI		0.089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
gMVP		0.49
Mutation Taster		=90/10	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: rs995264473; hg19: chr11-33891090;