rs1285470585

Variant names:

• chr2-74498306-G-C
• rs1285470585
• NM_001282430.2:c.218C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-74498306-G-C
• chr2-74498306-G-A
• chr2-74498306-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282430.2(LBX2):​c.218C>G​(p.Pro73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,544,742 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LBX2 NM_001282430.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0665527).

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.218C>G	p.Pro73Arg	missense	Exon 2 of 2	NP_001269359.1	Q6XYB7-1
	LBX2	NM_001009812.2		c.206C>G	p.Pro69Arg	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.218C>G	p.Pro73Arg	missense	Exon 2 of 2	ENSP00000366789.4	Q6XYB7-1
	LBX2	ENST00000460508.3	TSL:1	c.206C>G	p.Pro69Arg	missense	Exon 2 of 2	ENSP00000417116.2	Q6XYB7-2
	LBX2	ENST00000550249.2	TSL:1	n.512C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183088 AF XY: 0.00

Gnomad AFR exome AF: 0.0000807

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: 7.18e-7 AC: 1 AN: 1392496 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 685322

African (AFR) AF: 0.0000308 AC: 1 AN: 32454

American (AMR) AF: 0.00 AC: 0 AN: 40386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23046

East Asian (EAS) AF: 0.00 AC: 0 AN: 38806

South Asian (SAS) AF: 0.00 AC: 0 AN: 78090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080542

Other (OTH) AF: 0.00 AC: 0 AN: 57698

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.0000482 AC: 2 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15282

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: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000264

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	0.072
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.16
Sift	Benign	0.56	T
Sift4G	Benign	0.67	T
Polyphen		0.0010	B
Vest4		0.055
MutPred		0.21		Gain of MoRF binding (P = 0.0084)
MVP		0.27
MPC		0.89
ClinPred		0.066	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.40
Mutation Taster		=97/3	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: rs1285470585; hg19: chr2-74725433;