chr9-124012236-G-T

Variant names:

• chr9-124012236-G-T
• rs7868184
• NM_004789.4:c.-113G>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.-113G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,117,780 control chromosomes in the GnomAD database, including 2,565 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 0.077 (561 hom., cov: 32)
  • Exomes 𝑓: 0.061 (2004 hom.)
• Consequence: LHX2 NM_004789.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84
• Publications: 3 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX2	NM_004789.4	MANE Select	c.-113G>T		5_prime_UTR	Exon 1 of 5	NP_004780.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX2	ENST00000373615.9	TSL:1 MANE Select	c.-113G>T		5_prime_UTR	Exon 1 of 5	ENSP00000362717.4
	LHX2	ENST00000560961.2	TSL:3	c.-3-1725G>T		intron	N/A	ENSP00000453448.3
	LHX2	ENST00000446480.5	TSL:2	c.-122G>T		upstream_gene	N/A	ENSP00000394978.1

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11647 AN: 151584 Hom.: 562 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0716

GnomAD4 exome AF: 0.0606 AC: 58560 AN: 966086 Hom.: 2004 Cov.: 13 AF XY: 0.0613 AC XY: 28489 AN XY: 464514

African (AFR) AF: 0.134 AC: 2537 AN: 18940

American (AMR) AF: 0.0636 AC: 408 AN: 6418

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 930 AN: 11754

East Asian (EAS) AF: 0.0256 AC: 531 AN: 20740

South Asian (SAS) AF: 0.0996 AC: 2955 AN: 29676

European-Finnish (FIN) AF: 0.0570 AC: 1184 AN: 20756

Middle Eastern (MID) AF: 0.0770 AC: 192 AN: 2494

European-Non Finnish (NFE) AF: 0.0579 AC: 47382 AN: 817668

Other (OTH) AF: 0.0649 AC: 2441 AN: 37640

GnomAD4 genome AF: 0.0768 AC: 11656 AN: 151694 Hom.: 561 Cov.: 32 AF XY: 0.0760 AC XY: 5638 AN XY: 74138

African (AFR) AF: 0.135 AC: 5580 AN: 41454

American (AMR) AF: 0.0544 AC: 829 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0773 AC: 268 AN: 3468

East Asian (EAS) AF: 0.0281 AC: 144 AN: 5132

South Asian (SAS) AF: 0.0909 AC: 439 AN: 4828

European-Finnish (FIN) AF: 0.0432 AC: 452 AN: 10466

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0555 AC: 3761 AN: 67796

Other (OTH) AF: 0.0709 AC: 149 AN: 2102

Alfa AF: 0.0701 Hom.: 58

Bravo AF: 0.0798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.85
PhyloP100		2.8
PromoterAI		-0.065	Neutral
Mutation Taster		=297/3	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: rs7868184; hg19: chr9-126774515;