11-25077393-A-G

Position:

• chr11-25077393-A-G

Variant summary

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

The NM_001009909.4(LUZP2):​c.923A>G​(p.Glu308Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E308Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.750

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=0.14365745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUZP2	NM_001009909.4	c.923A>G	p.Glu308Gly	missense_variant	11/12	ENST00000336930.11	NP_001009909.2
LUZP2	NM_001252010.2	c.797A>G	p.Glu266Gly	missense_variant	9/10		NP_001238939.1
LUZP2	NM_001252008.2	c.665A>G	p.Glu222Gly	missense_variant	11/12		NP_001238937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUZP2	ENST00000336930.11	c.923A>G	p.Glu308Gly	missense_variant	11/12	1	NM_001009909.4	ENSP00000336817	P1
LUZP2	ENST00000533227.5	c.665A>G	p.Glu222Gly	missense_variant	11/12	1		ENSP00000432952
LUZP2	ENST00000620308.1	c.665A>G	p.Glu222Gly	missense_variant	10/11	5		ENSP00000480441

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

May 29, 2024

The c.923A>G (p.E308G) alteration is located in exon 11 (coding exon 11) of the LUZP2 gene. This alteration results from a A to G substitution at nucleotide position 923, causing the glutamic acid (E) at amino acid position 308 to be replaced by a glycine (G). 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	0.085
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.30	T;.;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.4	N;D;.
REVEL	Benign	0.11
Sift	Benign	0.039	D;D;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.28	B;.;.
Vest4		0.093
MutPred		0.058		Loss of stability (P = 0.1786);.;.;
MVP		0.49
MPC		0.067
ClinPred		0.29	T
GERP RS		3.9
Varity_R		0.069
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-25098939;