dbSNP rs1269061237: LUZP2:p.Val217Ile (chr11-24983177-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001009909.4(LUZP2):c.649G>A(p.Val217Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. V217F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LUZP2
NM_001009909.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.06

Variant links:

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]

LUZP2 links:

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ACMG classification

Classification made for transcript

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=0.25396907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP2	NM_001009909.4 link	c.649G>A	p.Val217Ile	missense_variant	Exon 9 of 12	ENST00000336930.11	NP_001009909.2	Q86TE4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LUZP2	ENST00000336930.11 link	c.649G>A	p.Val217Ile	missense_variant	Exon 9 of 12	1	NM_001009909.4	ENSP00000336817.6	Q86TE4-1
LUZP2	ENST00000533227.5 link	c.391G>A	p.Val131Ile	missense_variant	Exon 9 of 12	1		ENSP00000432952.1	Q86TE4-4
LUZP2	ENST00000620308.1 link	c.391G>A	p.Val131Ile	missense_variant	Exon 8 of 11	5		ENSP00000480441.1	Q86TE4-4
LUZP2	ENST00000529015.5 link	c.523G>A	p.Val175Ile	missense_variant	Exon 7 of 7	4		ENSP00000437032.1	E9PP05

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250542

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000205

AC:

AN:

1460424

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726522

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;.;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

T;T;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;.;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.61

N;N;N;.

REVEL

Benign

0.15

Sift

Benign

0.062

T;T;T;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.30

MutPred

0.15

Loss of loop (P = 0.1258);.;.;.;

MVP

0.36

MPC

0.33

ClinPred

0.89

GERP RS

5.5

Varity_R

0.12

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over