9-124014127-AGGACG-A

Position:

• chr9-124014127-AGGACG-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_004789.4(LHX2):​c.289_293del​(p.Asp97Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LHX2 NM_004789.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 10.0

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-124014127-AGGACG-A is Pathogenic according to our data. Variant chr9-124014127-AGGACG-A is described in ClinVar as [Pathogenic]. Clinvar id is 3342326.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-124014127-AGGACG-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX2	NM_004789.4	c.289_293del	p.Asp97Ter	frameshift_variant	2/5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4	c.289_293del	p.Asp97Ter	frameshift_variant	2/6		XP_006717386.1
LHX2	XM_047424082.1	c.289_293del	p.Asp97Ter	frameshift_variant	2/6		XP_047280038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX2	ENST00000373615.9	c.289_293del	p.Asp97Ter	frameshift_variant	2/5	1	NM_004789.4	ENSP00000362717	P1
LHX2	ENST00000446480.5	c.281_285del	p.Asp95Ter	frameshift_variant	2/5	2		ENSP00000394978
LHX2	ENST00000560961.2	c.166_170del	p.Asp56Ter	frameshift_variant	2/3	3		ENSP00000453448

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2023

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 37057675) -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-126776406;