rs1042486

Variant names:

• chr9-124021154-G-A
• rs1042486
• NM_004789.4:c.783G>A
• LHX2 p.Pro261Pro

Your query was ambiguous. Multiple possible variants found:

• chr9-124021154-G-A
• chr9-124021154-G-C
• chr9-124021154-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_004789.4(LHX2):​c.783G>A​(p.Pro261Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: LHX2 NM_004789.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 20 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.199).
• BP7: Synonymous conserved (PhyloP=-0.045 with no splicing effect.

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.783G>A	p.Pro261Pro	synonymous	Exon 4 of 5	NP_004780.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX2	ENST00000373615.9	TSL:1 MANE Select	c.783G>A	p.Pro261Pro	synonymous	Exon 4 of 5	ENSP00000362717.4	P50458
	LHX2	ENST00000446480.5	TSL:2	c.798G>A	p.Pro266Pro	synonymous	Exon 4 of 5	ENSP00000394978.1	H7C0H1
	LHX2	ENST00000488674.2	TSL:3	c.183G>A	p.Pro61Pro	synonymous	Exon 2 of 4	ENSP00000476200.1	U3KQT5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.0
DANN	Benign	0.93
PhyloP100		-0.045

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1042486;

hg19: chr9-126783433;