Variant chr9-124012460-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004789.4(LHX2):c.112A>G(p.Thr38Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000129 in 1,545,940 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

LHX2
NM_004789.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08133623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LHX2	NM_004789.4 linkuse as main transcript	c.112A>G	p.Thr38Ala	missense_variant	1/5	ENST00000373615.9
LHX2	XM_006717323.4 linkuse as main transcript	c.112A>G	p.Thr38Ala	missense_variant	1/6
LHX2	XM_047424082.1 linkuse as main transcript	c.112A>G	p.Thr38Ala	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LHX2	ENST00000373615.9 linkuse as main transcript	c.112A>G	p.Thr38Ala	missense_variant	1/5	1	NM_004789.4	P1
LHX2	ENST00000446480.5 linkuse as main transcript	c.106A>G	p.Thr36Ala	missense_variant	1/5	2
LHX2	ENST00000560961.2 linkuse as main transcript	c.-3-1501A>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1393788

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689990

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

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

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000174

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.112A>G (p.T38A) alteration is located in exon 1 (coding exon 1) of the LHX2 gene. This alteration results from a A to G substitution at nucleotide position 112, causing the threonine (T) at amino acid position 38 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.26

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.42

REVEL

Benign

0.20

Sift

Benign

0.26

Sift4G

Benign

0.44

Polyphen

0.0070

Vest4

0.19

MutPred

0.17

Gain of loop (P = 0.024);

MVP

0.76

MPC

1.2

ClinPred

0.053

GERP RS

3.9

Varity_R

0.065

gMVP

0.46

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