Variant 9-124021147-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004789.4(LHX2):c.776C>A(p.Pro259Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00494 in 1,614,200 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 33 hom. )

Consequence

LHX2
NM_004789.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067568123).

BP6

Variant 9-124021147-C-A is Benign according to our data. Variant chr9-124021147-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3042157.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LHX2	NM_004789.4 linkuse as main transcript	c.776C>A	p.Pro259Gln	missense_variant	4/5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4 linkuse as main transcript	c.776C>A	p.Pro259Gln	missense_variant	4/6		XP_006717386.1
LHX2	XM_047424082.1 linkuse as main transcript	c.776C>A	p.Pro259Gln	missense_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.776C>A	p.Pro259Gln	missense_variant	4/5	1	NM_004789.4	ENSP00000362717	P1
LHX2	ENST00000446480.5 linkuse as main transcript	c.794C>A	p.Pro265Gln	missense_variant	4/5	2		ENSP00000394978
LHX2	ENST00000488674.2 linkuse as main transcript	c.179C>A	p.Pro60Gln	missense_variant	2/4	3		ENSP00000476200

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

458

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00538

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00274

AC:

689

AN:

251366

Hom.:

AF XY:

0.00280

AC XY:

380

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00480

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00514

AC:

7510

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

3577

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00631

Gnomad4 OTH exome

AF:

0.00505

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152338

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

217

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00538

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00412

Hom.:

Bravo

AF:

0.00309

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00248

AC:

301

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00658

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LHX2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.32

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.082

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

M_CAP

Benign

0.022

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.74

MutationAssessor

Benign

-1.5

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.040

REVEL

Uncertain

0.31

Sift

Benign

0.43

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.12

MVP

0.47

MPC

1.0

ClinPred

0.014

GERP RS

4.4

Varity_R

0.10

gMVP

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over