rs2075064

Positions:

• chr9-124021568-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004789.4(LHX2):​c.933+264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,126 control chromosomes in the GnomAD database, including 11,232 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 0.36 (11232 hom., cov: 32)
• Consequence: LHX2 NM_004789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX2	NM_004789.4	c.933+264C>T		intron_variant		ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4	c.934-251C>T		intron_variant			XP_006717386.1
LHX2	XM_047424082.1	c.934-251C>T		intron_variant			XP_047280038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX2	ENST00000373615.9	c.933+264C>T		intron_variant		1	NM_004789.4	ENSP00000362717.4
LHX2	ENST00000446480.5	c.948+264C>T		intron_variant		2		ENSP00000394978.1
LHX2	ENST00000488674.2	c.334-251C>T		intron_variant		3		ENSP00000476200.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 54024 AN: 152008 Hom.: 11232 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 54018 AN: 152126 Hom.: 11232 Cov.: 32 AF XY: 0.356 AC XY: 26491 AN XY: 74354

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.356

Alfa AF: 0.417 Hom.: 13108

Bravo AF: 0.348

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs2075064; hg19: chr9-126783847;