Variant 9-124021136-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004789.4(LHX2):c.765C>T(p.Asp255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,614,130 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 133 hom. )

Consequence

LHX2
NM_004789.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.878

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 9-124021136-C-T is Benign according to our data. Variant chr9-124021136-C-T is described in ClinVar as [Benign]. Clinvar id is 770200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.878 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0626 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.765C>T	p.Asp255=	synonymous_variant	4/5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4 linkuse as main transcript	c.765C>T	p.Asp255=	synonymous_variant	4/6		XP_006717386.1
LHX2	XM_047424082.1 linkuse as main transcript	c.765C>T	p.Asp255=	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.765C>T	p.Asp255=	synonymous_variant	4/5	1	NM_004789.4	ENSP00000362717	P1
LHX2	ENST00000446480.5 linkuse as main transcript	c.783C>T	p.Asp261=	synonymous_variant	4/5	2		ENSP00000394978
LHX2	ENST00000488674.2 linkuse as main transcript	c.168C>T	p.Asp56=	synonymous_variant	2/4	3		ENSP00000476200

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

539

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0273

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0123

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.0107

AC:

2676

AN:

251048

Hom.:

AF XY:

0.00797

AC XY:

1082

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.0701

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00941

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00262

AC:

3823

AN:

1461790

Hom.:

133

Cov.:

AF XY:

0.00228

AC XY:

1661

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.0646

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0174

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00354

AC:

539

AN:

152340

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

273

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.0273

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0123

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.00657

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 27, 2018	- -

LHX2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.5

DANN

Benign

0.93

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