Genetic Variant NM_001282430.2:c.387G>C (chr2-74498137-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001282430.2(LBX2):c.387G>C(p.Val129Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,528 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LBX2
NM_001282430.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.276

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-74498137-C-G is Benign according to our data. Variant chr2-74498137-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 754328.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.276 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBX2	NM_001282430.2 link	c.387G>C	p.Val129Val	synonymous_variant	Exon 2 of 2	ENST00000377566.9	NP_001269359.1	Q6XYB7-1
LBX2	NM_001009812.2 link	c.375G>C	p.Val125Val	synonymous_variant	Exon 2 of 2		NP_001009812.1	Q6XYB7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LBX2	ENST00000377566.9 link	c.387G>C	p.Val129Val	synonymous_variant	Exon 2 of 2	1	NM_001282430.2	ENSP00000366789.4	Q6XYB7-1
LBX2	ENST00000460508.3 link	c.375G>C	p.Val125Val	synonymous_variant	Exon 2 of 2	1		ENSP00000417116.2	Q6XYB7-2
LBX2	ENST00000550249.2 link	n.681G>C		non_coding_transcript_exon_variant	Exon 3 of 3	1
LBX2	ENST00000341396 link	c.*32G>C		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000450229.1	G3V218

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249806

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725816

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.8

DANN

Benign

0.91

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

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