chr2-74497982-G-A

Variant names:

• chr2-74497982-G-A
• rs747140609
• NM_001282430.2:c.542C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001282430.2(LBX2):​c.542C>T​(p.Ala181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,605,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: LBX2 NM_001282430.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07356611).

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.542C>T	p.Ala181Val	missense	Exon 2 of 2	NP_001269359.1	Q6XYB7-1
	LBX2	NM_001009812.2		c.530C>T	p.Ala177Val	missense	Exon 2 of 2	NP_001009812.1	Q6XYB7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBX2	ENST00000377566.9	TSL:1 MANE Select	c.542C>T	p.Ala181Val	missense	Exon 2 of 2	ENSP00000366789.4	Q6XYB7-1
	LBX2	ENST00000460508.3	TSL:1	c.530C>T	p.Ala177Val	missense	Exon 2 of 2	ENSP00000417116.2	Q6XYB7-2
	LBX2	ENST00000550249.2	TSL:1	n.836C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152282 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000142 AC: 35 AN: 246590 AF XY: 0.000165

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000264

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000114 AC: 166 AN: 1453342 Hom.: 0 Cov.: 29 AF XY: 0.000112 AC XY: 81 AN XY: 721538

African (AFR) AF: 0.0000301 AC: 1 AN: 33266

American (AMR) AF: 0.000227 AC: 10 AN: 44108

Ashkenazi Jewish (ASJ) AF: 0.000270 AC: 7 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.000221 AC: 19 AN: 85794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.000114 AC: 126 AN: 1106188

Other (OTH) AF: 0.0000501 AC: 3 AN: 59858

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74406

African (AFR) AF: 0.00 AC: 0 AN: 41484

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	4.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.14
Sift	Benign	0.031	D
Sift4G	Benign	0.16	T
Polyphen		0.019	B
Vest4		0.049
MutPred		0.26		Loss of catalytic residue at A181 (P = 0.0649)
MVP		0.53
MPC		0.49
ClinPred		0.033	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
gMVP		0.27
Mutation Taster		=98/2	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: rs747140609; hg19: chr2-74725109;