Genetic Variant LBX2:p.Gly72Arg (chr2-74498310-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001282430.2(LBX2):c.214G>C(p.Gly72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,539,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

LBX2
NM_001282430.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Publications

0 publications found

Variant links:

Genes affected

LBX2 (HGNC:15525): (ladybird homeobox 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including muscle cell differentiation; positive regulation of convergent extension involved in gastrulation; and positive regulation of non-canonical Wnt signaling pathway. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LBX2 links:

LBX2-AS1 (HGNC:25136): (LBX2 antisense RNA 1)

LBX2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015339613).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282430.2. 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
	LBX2	NM_001282430.2	MANE Select	c.214G>C	p.Gly72Arg	missense	Exon 2 of 2	NP_001269359.1	Q6XYB7-1
	LBX2	NM_001009812.2		c.202G>C	p.Gly68Arg	missense	Exon 2 of 2	NP_001009812.1	Q6XYB7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LBX2	ENST00000377566.9	TSL:1 MANE Select	c.214G>C	p.Gly72Arg	missense	Exon 2 of 2	ENSP00000366789.4	Q6XYB7-1
LBX2	ENST00000460508.3	TSL:1	c.202G>C	p.Gly68Arg	missense	Exon 2 of 2	ENSP00000417116.2	Q6XYB7-2
LBX2	ENST00000550249.2	TSL:1	n.508G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000278

AC:

AN:

176364

AF XY:

0.000218

show subpopulations

Gnomad AFR exome

AF:

0.000165

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000294

Gnomad OTH exome

AF:

0.000449

GnomAD4 exome

AF:

0.000187

AC:

259

AN:

1386722

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

118

AN XY:

681972

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

32234

American (AMR)

AF:

0.000762

AC:

AN:

39380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22672

East Asian (EAS)

AF:

0.00

AC:

AN:

38702

South Asian (SAS)

AF:

0.0000904

AC:

AN:

77412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36366

Middle Eastern (MID)

AF:

0.00305

AC:

AN:

4592

European-Non Finnish (NFE)

AF:

0.000159

AC:

171

AN:

1077928

Other (OTH)

AF:

0.000522

AC:

AN:

57436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

0.000335

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41574

American (AMR)

AF:

0.00131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68044

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000300

Hom.:

Bravo

AF:

0.000419

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000250

AC:

ExAC

AF:

0.000230

AC:

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

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.19

M_CAP

Benign

0.020

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.1

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

REVEL

Benign

0.090

Sift

Benign

0.18

Sift4G

Benign

0.24

Polyphen

0.054

Vest4

0.12

MVP

0.37

MPC

0.88

ClinPred

0.041

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.052

gMVP

0.46

Mutation Taster

=93/7

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