rs200569816

Variant names:

• chr11-24983201-C-G
• rs200569816
• NM_001009909.4:c.673C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-24983201-C-G
• chr11-24983201-C-A
• chr11-24983201-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001009909.4(LUZP2):​c.673C>G​(p.Pro225Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,612,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.260
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031715423).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009909.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUZP2	NM_001009909.4	MANE Select	c.673C>G	p.Pro225Ala	missense	Exon 9 of 12	NP_001009909.2	Q86TE4-1
	LUZP2	NM_001252010.2		c.547C>G	p.Pro183Ala	missense	Exon 7 of 10	NP_001238939.1
	LUZP2	NM_001252008.2		c.415C>G	p.Pro139Ala	missense	Exon 9 of 12	NP_001238937.1	Q86TE4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUZP2	ENST00000336930.11	TSL:1 MANE Select	c.673C>G	p.Pro225Ala	missense	Exon 9 of 12	ENSP00000336817.6	Q86TE4-1
	LUZP2	ENST00000533227.5	TSL:1	c.415C>G	p.Pro139Ala	missense	Exon 9 of 12	ENSP00000432952.1	Q86TE4-4
	LUZP2	ENST00000620308.1	TSL:5	c.415C>G	p.Pro139Ala	missense	Exon 8 of 11	ENSP00000480441.1	Q86TE4-4

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151686 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250636 AF XY: 0.0000591

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 55 AN: 1460470 Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30 AN XY: 726544

African (AFR) AF: 0.000330 AC: 11 AN: 33366

American (AMR) AF: 0.0000224 AC: 1 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39678

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111070

Other (OTH) AF: 0.0000166 AC: 1 AN: 60324

GnomAD4 genome AF: 0.0000659 AC: 10 AN: 151802 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74204

African (AFR) AF: 0.000145 AC: 6 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67814

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.28
DANN	Benign	0.42
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.26
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.014
Sift	Benign	0.53	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.16
MPC		0.055
ClinPred		0.014	T
GERP RS		-2.1
Varity_R		0.025
gMVP		0.074
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200569816; hg19: chr11-25004747;