chr9-124013971-C-A

Position:

• chr9-124013971-C-A

Variant summary

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

The NM_004789.4(LHX2):​c.131C>A​(p.Ser44Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LHX2 NM_004789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30

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=0.41978297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX2	NM_004789.4	c.131C>A	p.Ser44Tyr	missense_variant	2/5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4	c.131C>A	p.Ser44Tyr	missense_variant	2/6		XP_006717386.1
LHX2	XM_047424082.1	c.131C>A	p.Ser44Tyr	missense_variant	2/6		XP_047280038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX2	ENST00000373615.9	c.131C>A	p.Ser44Tyr	missense_variant	2/5	1	NM_004789.4	ENSP00000362717.4
LHX2	ENST00000446480.5	c.122C>A	p.Ser41Tyr	missense_variant	2/5	2		ENSP00000394978.1
LHX2	ENST00000560961.2	c.8C>A	p.Ser3Tyr	missense_variant	2/3	3		ENSP00000453448.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 08, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	.;D
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.16	T;D
Sift4G	Uncertain	0.034	D;T
Polyphen		0.39	.;B
Vest4		0.31
MutPred		0.33		.;Loss of disorder (P = 0.02);
MVP		0.60
MPC		1.7
ClinPred		0.78	D
GERP RS		5.9
Varity_R		0.23
gMVP		0.64

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: chr9-126776250;