Variant 2-74498048-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282430.2(LBX2):c.476C>T(p.Pro159Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000142 in 1,613,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

LBX2
NM_001282430.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

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 (HGNC:):

LBX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2117056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBX2	NM_001282430.2 linkuse as main transcript	c.476C>T	p.Pro159Leu	missense_variant	2/2	ENST00000377566.9	NP_001269359.1	Q6XYB7-1
LBX2	NM_001009812.2 linkuse as main transcript	c.464C>T	p.Pro155Leu	missense_variant	2/2		NP_001009812.1	Q6XYB7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LBX2	ENST00000377566.9 linkuse as main transcript	c.476C>T	p.Pro159Leu	missense_variant	2/2	1	NM_001282430.2	ENSP00000366789.4	Q6XYB7-1
LBX2	ENST00000460508.3 linkuse as main transcript	c.464C>T	p.Pro155Leu	missense_variant	2/2	1		ENSP00000417116.2	Q6XYB7-2
LBX2	ENST00000550249.2 linkuse as main transcript	n.770C>T		non_coding_transcript_exon_variant	3/3	1
LBX2	ENST00000341396.2 linkuse as main transcript	c.*121C>T		3_prime_UTR_variant	2/2	3		ENSP00000450229.1	G3V218

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000679

AC:

AN:

250418

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

213

AN:

1461204

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000105

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000156

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.464C>T (p.P155L) alteration is located in exon 2 (coding exon 2) of the LBX2 gene. This alteration results from a C to T substitution at nucleotide position 464, causing the proline (P) at amino acid position 155 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

T;T

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.21

T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.98

D;D

Vest4

0.097

MVP

0.69

MPC

1.4

ClinPred

0.41

GERP RS

4.8

Varity_R

0.24

gMVP

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over