11-24976606-G-C

Variant names:

• chr11-24976606-G-C
• rs746580810
• NM_001009909.4:c.538G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001009909.4(LUZP2):​c.538G>C​(p.Asp180His) variant causes a missense change. The variant allele was found at a frequency of 0.0000292 in 1,438,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D180N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34837207).

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.538G>C	p.Asp180His	missense	Exon 8 of 12	NP_001009909.2	Q86TE4-1
	LUZP2	NM_001252010.2		c.412G>C	p.Asp138His	missense	Exon 6 of 10	NP_001238939.1
	LUZP2	NM_001252008.2		c.280G>C	p.Asp94His	missense	Exon 8 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.538G>C	p.Asp180His	missense	Exon 8 of 12	ENSP00000336817.6	Q86TE4-1
	LUZP2	ENST00000533227.5	TSL:1	c.280G>C	p.Asp94His	missense	Exon 8 of 12	ENSP00000432952.1	Q86TE4-4
	LUZP2	ENST00000620308.1	TSL:5	c.280G>C	p.Asp94His	missense	Exon 7 of 11	ENSP00000480441.1	Q86TE4-4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.0000302 AC: 7 AN: 232012 AF XY: 0.0000317

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000332

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000560

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000292 AC: 42 AN: 1438742 Hom.: 0 Cov.: 30 AF XY: 0.0000335 AC XY: 24 AN XY: 715978

African (AFR) AF: 0.00 AC: 0 AN: 31512

American (AMR) AF: 0.0000489 AC: 2 AN: 40924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25376

East Asian (EAS) AF: 0.00 AC: 0 AN: 38180

South Asian (SAS) AF: 0.00 AC: 0 AN: 83480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.0000336 AC: 37 AN: 1101680

Other (OTH) AF: 0.0000506 AC: 3 AN: 59248

GnomAD4 genome Cov.: 28

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.083		Loss of ubiquitination at K184 (P = 0.0517)
MVP		0.61
MPC		0.39
ClinPred		0.80	D
GERP RS		5.2
Varity_R		0.49
gMVP		0.41
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs746580810; hg19: chr11-24998152;