rs1859167678

Variant names:

• chr9-124015379-C-A
• NM_004789.4:c.581C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-124015379-C-A
• chr9-124015379-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004789.4(LHX2):​c.581C>A​(p.Ala194Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A194G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LHX2 NM_004789.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33365715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHX2	NM_004789.4	c.581C>A	p.Ala194Glu	missense_variant	Exon 3 of 5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4	c.581C>A	p.Ala194Glu	missense_variant	Exon 3 of 6		XP_006717386.1
LHX2	XM_047424082.1	c.581C>A	p.Ala194Glu	missense_variant	Exon 3 of 6		XP_047280038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHX2	ENST00000373615.9	c.581C>A	p.Ala194Glu	missense_variant	Exon 3 of 5	1	NM_004789.4	ENSP00000362717.4
LHX2	ENST00000446480.5	c.596C>A	p.Ala199Glu	missense_variant	Exon 3 of 5	2		ENSP00000394978.1
LHX2	ENST00000488674.2	c.-20C>A		upstream_gene_variant		3		ENSP00000476200.1
LHX2	ENST00000560961.2	c.*18C>A		downstream_gene_variant		3		ENSP00000453448.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457594 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724696

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.74
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.49	N
REVEL	Uncertain	0.37
Sift	Benign	0.82	T
Sift4G	Benign	1.0	T
Polyphen		0.20	B
Vest4		0.46
MutPred		0.43		Gain of solvent accessibility (P = 0.0456);
MVP		0.81
MPC		1.4
ClinPred		0.15	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-126777658;