Genetic Variant LBX2:p.Asp197Asn (chr2-74497935-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001282430.2(LBX2):c.589G>A(p.Asp197Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000778 in 1,414,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D197H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

LBX2
NM_001282430.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.714

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:

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ACMG classification

Classification was made for transcript

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=0.3071434).

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.589G>A	p.Asp197Asn	missense	Exon 2 of 2	NP_001269359.1	Q6XYB7-1
	LBX2	NM_001009812.2		c.577G>A	p.Asp193Asn	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.589G>A	p.Asp197Asn	missense	Exon 2 of 2	ENSP00000366789.4	Q6XYB7-1
LBX2	ENST00000460508.3	TSL:1	c.577G>A	p.Asp193Asn	missense	Exon 2 of 2	ENSP00000417116.2	Q6XYB7-2
LBX2	ENST00000550249.2	TSL:1	n.883G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000464

AC:

AN:

215430

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000778

AC:

AN:

1414500

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

698252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31940

American (AMR)

AF:

0.00

AC:

AN:

37718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23536

East Asian (EAS)

AF:

0.00

AC:

AN:

38910

South Asian (SAS)

AF:

0.000136

AC:

AN:

80688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5456

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086404

Other (OTH)

AF:

0.00

AC:

AN:

58008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0089

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.43

MutationAssessor

Benign

1.8

PhyloP100

0.71

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Uncertain

0.016

Sift4G

Uncertain

0.021

Polyphen

0.99

Vest4

0.12

MutPred

0.28

Loss of stability (P = 0.4223)

MVP

0.72

MPC

1.1

ClinPred

0.95

GERP RS

4.9

Varity_R

0.11

gMVP

0.50

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over