9-124021568-C-T

Variant names:

• chr9-124021568-C-T
• rs2075064
• NM_004789.4:c.933+264C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004789.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX2	NM_004789.4	MANE Select	c.933+264C>T		intron	N/A	NP_004780.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX2	ENST00000373615.9	TSL:1 MANE Select	c.933+264C>T		intron	N/A	ENSP00000362717.4	P50458
	LHX2	ENST00000446480.5	TSL:2	c.948+264C>T		intron	N/A	ENSP00000394978.1	H7C0H1
	LHX2	ENST00000488674.2	TSL:3	c.334-251C>T		intron	N/A	ENSP00000476200.1	U3KQT5

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

African (AFR) AF: 0.125 AC: 5209 AN: 41532

American (AMR) AF: 0.473 AC: 7224 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.424 AC: 2196 AN: 5176

South Asian (SAS) AF: 0.323 AC: 1558 AN: 4822

European-Finnish (FIN) AF: 0.485 AC: 5120 AN: 10556

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30279 AN: 67974

Other (OTH) AF: 0.356 AC: 753 AN: 2116

Alfa AF: 0.407 Hom.: 18969

Bravo AF: 0.348

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.64
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075064; hg19: chr9-126783847;