NM_001009909.4:c.656G>C

Variant names:

• chr11-24983184-G-C
• rs141562546
• NM_001009909.4:c.656G>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.656G>C​(p.Arg219Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R219H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777
• Publications: 4 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=0.37146065).

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.656G>C	p.Arg219Pro	missense	Exon 9 of 12	NP_001009909.2	Q86TE4-1
	LUZP2	NM_001252010.2		c.530G>C	p.Arg177Pro	missense	Exon 7 of 10	NP_001238939.1
	LUZP2	NM_001252008.2		c.398G>C	p.Arg133Pro	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.656G>C	p.Arg219Pro	missense	Exon 9 of 12	ENSP00000336817.6	Q86TE4-1
	LUZP2	ENST00000533227.5	TSL:1	c.398G>C	p.Arg133Pro	missense	Exon 9 of 12	ENSP00000432952.1	Q86TE4-4
	LUZP2	ENST00000620308.1	TSL:5	c.398G>C	p.Arg133Pro	missense	Exon 8 of 11	ENSP00000480441.1	Q86TE4-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
PhyloP100		0.78
Varity_R		0.68
gMVP		0.36
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs141562546; hg19: chr11-25004730;