11-24983277-C-T

Variant names:

• chr11-24983277-C-T
• NM_001009909.4:c.749C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009909.4(LUZP2):​c.749C>T​(p.Ala250Val) 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. 15/21 in silico tools predict 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: 0.767

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076972395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP2	NM_001009909.4	c.749C>T	p.Ala250Val	missense_variant	Exon 9 of 12	ENST00000336930.11	NP_001009909.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUZP2	ENST00000336930.11	c.749C>T	p.Ala250Val	missense_variant	Exon 9 of 12	1	NM_001009909.4	ENSP00000336817.6
LUZP2	ENST00000533227.5	c.491C>T	p.Ala164Val	missense_variant	Exon 9 of 12	1		ENSP00000432952.1
LUZP2	ENST00000620308.1	c.491C>T	p.Ala164Val	missense_variant	Exon 8 of 11	5		ENSP00000480441.1
LUZP2	ENST00000529015.5	c.*95C>T		downstream_gene_variant		4		ENSP00000437032.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.749C>T (p.A250V) alteration is located in exon 9 (coding exon 9) of the LUZP2 gene. This alteration results from a C to T substitution at nucleotide position 749, causing the alanine (A) at amino acid position 250 to be replaced by a valine (V). 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	Benign	0.089
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.6
DANN	Benign	0.84
DEOGEN2	Benign	0.047	T;.;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.51	T;.;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.20	N;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.76	N;N;.
REVEL	Benign	0.037
Sift	Benign	0.15	T;T;.
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0050	B;.;.
Vest4		0.077
MutPred		0.10		Loss of glycosylation at P248 (P = 0.0634);.;.;
MVP		0.048
MPC		0.072
ClinPred		0.061	T
GERP RS		1.2
Varity_R		0.044
gMVP		0.22

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: chr11-25004823; COSMIC: COSV61199878; COSMIC: COSV61199878;