11-24983232-G-T

Variant names:

• chr11-24983232-G-T
• rs139865032
• NM_001009909.4:c.704G>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.704G>T​(p.Arg235Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R235Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

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=0.073049456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP2	NM_001009909.4	c.704G>T	p.Arg235Leu	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.704G>T	p.Arg235Leu	missense_variant	Exon 9 of 12	1	NM_001009909.4	ENSP00000336817.6
LUZP2	ENST00000533227.5	c.446G>T	p.Arg149Leu	missense_variant	Exon 9 of 12	1		ENSP00000432952.1
LUZP2	ENST00000620308.1	c.446G>T	p.Arg149Leu	missense_variant	Exon 8 of 11	5		ENSP00000480441.1
LUZP2	ENST00000529015.5	c.*50G>T		downstream_gene_variant		4		ENSP00000437032.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250530 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135390

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460344 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.35	T;.;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.4	N;D;.
REVEL	Benign	0.064
Sift	Benign	0.030	D;D;.
Sift4G	Benign	0.080	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.089
MutPred		0.14		Loss of MoRF binding (P = 0.0626);.;.;
MVP		0.14
MPC		0.071
ClinPred		0.18	T
GERP RS		0.037
Varity_R		0.12
gMVP		0.14

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: rs139865032; hg19: chr11-25004778; COSMIC: COSV61204685; COSMIC: COSV61204685;