11-24738270-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001009909.4(LUZP2):c.301A>G(p.Thr101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029064536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LUZP2	NM_001009909.4	c.301A>G	p.Thr101Ala	missense_variant	4/12	ENST00000336930.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LUZP2	ENST00000336930.11	c.301A>G	p.Thr101Ala	missense_variant	4/12	1	NM_001009909.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250652 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135472

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460452 Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6 AN XY: 726566

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Sep 12, 2023

The c.301A>G (p.T101A) alteration is located in exon 4 (coding exon 4) of the LUZP2 gene. This alteration results from a A to G substitution at nucleotide position 301, causing the threonine (T) at amino acid position 101 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	13
Dann	Benign	0.95
DEOGEN2	Benign	0.12	T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.73	T;T;.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.029	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N;.;.;.
MutationTaster	Benign	0.95	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N;N;N;.
REVEL	Benign	0.091
Sift	Benign	0.71	T;T;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.016	B;.;.;.
Vest4		0.21
MutPred		0.049		Loss of phosphorylation at T101 (P = 0.0533);Loss of phosphorylation at T101 (P = 0.0533);.;.;
MVP		0.13
MPC		0.056
ClinPred		0.082	T
GERP RS		2.1
Varity_R		0.065
gMVP		0.036

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

LitVar

Other links and lift over

dbSNP: rs753486369; hg19: chr11-24759816;