11-24983151-A-T

Position:

• chr11-24983151-A-T

Variant summary

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

The NM_001009909.4(LUZP2):​c.623A>T​(p.Glu208Val) 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: 32)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28

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=0.33965474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LUZP2	NM_001009909.4	c.623A>T	p.Glu208Val	missense_variant	9/12	ENST00000336930.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LUZP2	ENST00000336930.11	c.623A>T	p.Glu208Val	missense_variant	9/12	1	NM_001009909.4	P1
LUZP2	ENST00000533227.5	c.365A>T	p.Glu122Val	missense_variant	9/12	1
LUZP2	ENST00000620308.1	c.365A>T	p.Glu122Val	missense_variant	8/11	5
LUZP2	ENST00000529015.5	c.497A>T	p.Glu166Val	missense_variant	7/7	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Nov 08, 2022

The c.623A>T (p.E208V) alteration is located in exon 9 (coding exon 9) of the LUZP2 gene. This alteration results from a A to T substitution at nucleotide position 623, causing the glutamic acid (E) at amino acid position 208 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	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;T;.;.
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D;.;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L;.;.;.
MutationTaster	Benign	0.75	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.3	D;D;D;.
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.79
MutPred		0.16		Loss of ubiquitination at K204 (P = 0.0272);.;.;.;
MVP		0.50
MPC		0.38
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1856087835; hg19: chr11-25004697;