Genetic Variant NM_005574.4:c.50C>G (chr11-33869544-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005574.4(LMO2):c.50C>G(p.Pro17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000628 in 1,273,784 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

LMO2
NM_005574.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

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]

LMO2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22036514).

BS2

High AC in GnomAd4 at 54 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMO2	NM_005574.4	MANE Select	c.50C>G	p.Pro17Arg	missense	Exon 4 of 6	NP_005565.2	P25791-3
LMO2	NM_001142315.2		c.-158C>G		5_prime_UTR	Exon 2 of 4	NP_001135787.1	P25791-1
LMO2	NM_001142316.2		c.-158C>G		5_prime_UTR	Exon 1 of 3	NP_001135788.1	P25791-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMO2	ENST00000257818.3	TSL:1 MANE Select	c.50C>G	p.Pro17Arg	missense	Exon 4 of 6	ENSP00000257818.2	P25791-3
LMO2	ENST00000395833.7	TSL:1	c.-158C>G		5_prime_UTR	Exon 1 of 3	ENSP00000379175.3	P25791-1
LMO2	ENST00000969327.1		c.50C>G	p.Pro17Arg	missense	Exon 3 of 5	ENSP00000639386.1

Frequencies

GnomAD3 genomes

AF:

0.000363

AC:

AN:

148750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

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

AF:

0.0000231

AC:

AN:

1124926

Hom.:

Cov.:

AF XY:

0.0000200

AC XY:

AN XY:

548996

show subpopulations

African (AFR)

AF:

0.000939

AC:

AN:

21294

American (AMR)

AF:

0.00

AC:

AN:

11516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15570

East Asian (EAS)

AF:

0.00

AC:

AN:

21406

South Asian (SAS)

AF:

0.0000726

AC:

AN:

41302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3672

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

931402

Other (OTH)

AF:

0.0000709

AC:

AN:

42336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000363

AC:

AN:

148858

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

AN XY:

72658

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

41138

American (AMR)

AF:

0.000133

AC:

AN:

15006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

5086

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66766

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000291

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Benign

0.97

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.97

PhyloP100

1.1

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.4

REVEL

Benign

0.071

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.017

Polyphen

0.89

Vest4

0.092

MutPred

0.34

Loss of glycosylation at P17 (P = 0.0203)

MVP

0.13

MPC

0.80

ClinPred

0.51

GERP RS

2.8

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

gMVP

0.47

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over