Variant 9-124021154-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004789.4(LHX2):c.783G>C(p.Pro261=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,834 control chromosomes in the GnomAD database, including 160,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 12371 hom., cov: 32)

Exomes 𝑓: 0.45 ( 148320 hom. )

Consequence

LHX2
NM_004789.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0450

Variant links:

Genes affected

LHX2 (HGNC:6594): (LIM homeobox 2) This gene encodes a protein belonging to a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein may function as a transcriptional regulator. The protein can recapitulate or rescue phenotypes in Drosophila caused by a related protein, suggesting conservation of function during evolution. [provided by RefSeq, Jul 2008]

LHX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=-0.045 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LHX2	NM_004789.4 linkuse as main transcript	c.783G>C	p.Pro261=	synonymous_variant	4/5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4 linkuse as main transcript	c.783G>C	p.Pro261=	synonymous_variant	4/6		XP_006717386.1
LHX2	XM_047424082.1 linkuse as main transcript	c.783G>C	p.Pro261=	synonymous_variant	4/6		XP_047280038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LHX2	ENST00000373615.9 linkuse as main transcript	c.783G>C	p.Pro261=	synonymous_variant	4/5	1	NM_004789.4	ENSP00000362717	P1
LHX2	ENST00000446480.5 linkuse as main transcript	c.801G>C	p.Pro267=	synonymous_variant	4/5	2		ENSP00000394978
LHX2	ENST00000488674.2 linkuse as main transcript	c.186G>C	p.Pro62=	synonymous_variant	2/4	3		ENSP00000476200

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59352

AN:

151946

Hom.:

12364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.494

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.433

AC:

108766

AN:

251210

Hom.:

24821

AF XY:

0.426

AC XY:

57843

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.426

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.451

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.445

AC:

650880

AN:

1461770

Hom.:

148320

Cov.:

AF XY:

0.440

AC XY:

320187

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.570

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.391

AC:

59392

AN:

152064

Hom.:

12371

Cov.:

AF XY:

0.389

AC XY:

28931

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.485

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.384

Alfa

AF:

0.410

Hom.:

2418

Bravo

AF:

0.386

Asia WGS

AF:

0.373

AC:

1294

AN:

3478

EpiCase

AF:

0.435

EpiControl

AF:

0.427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.68

DANN

Benign

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over