11-24914534-T-G

Variant names:

• chr11-24914534-T-G
• rs144319132
• NM_001009909.4:c.518T>G

Variant summary

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

The NM_001009909.4(LUZP2):​c.518T>G​(p.Phe173Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. F173Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• Publications: 0 publications found

Genes affected

LUZP2 (HGNC:23206): (leucine zipper protein 2) This gene encodes a leucine zipper protein. This protein is deleted in some patients with Wilms tumor-Aniridia-Genitourinary anomalies-mental Retardation (WAGR) syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009909.4. 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
	LUZP2	NM_001009909.4	MANE Select	c.518T>G	p.Phe173Cys	missense	Exon 7 of 12	NP_001009909.2	Q86TE4-1
	LUZP2	NM_001252008.2		c.260T>G	p.Phe87Cys	missense	Exon 7 of 12	NP_001238937.1	Q86TE4-4
	LUZP2	NM_001252010.2		c.397-62057T>G		intron	N/A	NP_001238939.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUZP2	ENST00000336930.11	TSL:1 MANE Select	c.518T>G	p.Phe173Cys	missense	Exon 7 of 12	ENSP00000336817.6	Q86TE4-1
	LUZP2	ENST00000533227.5	TSL:1	c.260T>G	p.Phe87Cys	missense	Exon 7 of 12	ENSP00000432952.1	Q86TE4-4
	LUZP2	ENST00000620308.1	TSL:5	c.260T>G	p.Phe87Cys	missense	Exon 6 of 11	ENSP00000480441.1	Q86TE4-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.067	T
Polyphen		0.0090	B
Vest4		0.76
MutPred		0.30		Gain of methylation at K174 (P = 0.0909)
MVP		0.32
MPC		0.42
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.28
gMVP		0.31
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs144319132; hg19: chr11-24936080;