11-24729238-G-C

Variant summary

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

The NM_001009909.4(LUZP2):c.132G>C(p.Gln44His) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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

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=0.29225233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LUZP2	NM_001009909.4	c.132G>C	p.Gln44His	missense_variant	2/12	ENST00000336930.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LUZP2	ENST00000336930.11	c.132G>C	p.Gln44His	missense_variant	2/12	1	NM_001009909.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.132G>C (p.Q44H) alteration is located in exon 2 (coding exon 2) of the LUZP2 gene. This alteration results from a G to C substitution at nucleotide position 132, causing the glutamine (Q) at amino acid position 44 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	0.52	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.13
Sift	Benign	0.076	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.99	D;.
Vest4		0.47
MutPred		0.16		Loss of disorder (P = 0.1226);Loss of disorder (P = 0.1226);
MVP		0.42
MPC		0.061
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.23
gMVP		0.42

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: chr11-24750784;