Variant chr9-124014131-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_004789.4(LHX2):c.291C>T(p.Asp97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,613,466 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 11 hom. )

Consequence

LHX2
NM_004789.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0410

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 9-124014131-C-T is Benign according to our data. Variant chr9-124014131-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056509.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.041 with no splicing effect.

BS2

High AC in GnomAd4 at 413 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LHX2	NM_004789.4 linkuse as main transcript	c.291C>T	p.Asp97=	synonymous_variant	2/5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4 linkuse as main transcript	c.291C>T	p.Asp97=	synonymous_variant	2/6		XP_006717386.1
LHX2	XM_047424082.1 linkuse as main transcript	c.291C>T	p.Asp97=	synonymous_variant	2/6		XP_047280038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LHX2	ENST00000373615.9 linkuse as main transcript	c.291C>T	p.Asp97=	synonymous_variant	2/5	1	NM_004789.4	ENSP00000362717	P1
LHX2	ENST00000446480.5 linkuse as main transcript	c.285C>T	p.Asp95=	synonymous_variant	2/5	2		ENSP00000394978
LHX2	ENST00000560961.2 linkuse as main transcript	c.168C>T	p.Asp56=	synonymous_variant	2/3	3		ENSP00000453448

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

413

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00362

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00252

AC:

630

AN:

250462

Hom.:

AF XY:

0.00239

AC XY:

324

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.000865

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00407

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00381

AC:

5565

AN:

1461164

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

2635

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00458

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00271

AC:

413

AN:

152302

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00362

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00340

Hom.:

Bravo

AF:

0.00292

EpiCase

AF:

0.00431

EpiControl

AF:

0.00433

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

Aug 15, 2019

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

BayesDel_noAF

Benign

-0.41

CADD

Benign

2.2

DANN

Benign

0.83

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