11-25077339-C-G

Variant names:

• chr11-25077339-C-G
• rs201686624
• NM_001009909.4:c.869C>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.869C>G​(p.Pro290Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P290L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=0.11274493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP2	NM_001009909.4	c.869C>G	p.Pro290Arg	missense_variant	Exon 11 of 12	ENST00000336930.11	NP_001009909.2
LUZP2	NM_001252010.2	c.743C>G	p.Pro248Arg	missense_variant	Exon 9 of 10		NP_001238939.1
LUZP2	NM_001252008.2	c.611C>G	p.Pro204Arg	missense_variant	Exon 11 of 12		NP_001238937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUZP2	ENST00000336930.11	c.869C>G	p.Pro290Arg	missense_variant	Exon 11 of 12	1	NM_001009909.4	ENSP00000336817.6
LUZP2	ENST00000533227.5	c.611C>G	p.Pro204Arg	missense_variant	Exon 11 of 12	1		ENSP00000432952.1
LUZP2	ENST00000620308.1	c.611C>G	p.Pro204Arg	missense_variant	Exon 10 of 11	5		ENSP00000480441.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251382 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459686 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726252

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000563

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.7
DANN	Benign	0.74
DEOGEN2	Benign	0.020	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.25	T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.36	N;N;.
REVEL	Benign	0.049
Sift	Uncertain	0.016	D;D;.
Sift4G	Uncertain	0.031	D;D;D
Polyphen		0.0	B;.;.
Vest4		0.063
MutPred		0.14		Gain of MoRF binding (P = 0.0454);.;.;
MVP		0.13
MPC		0.058
ClinPred		0.052	T
GERP RS		-0.53
Varity_R		0.037
gMVP		0.15

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: rs201686624; hg19: chr11-25098885;