chr10-101002687-C-T

Variant names:

• chr10-101002687-C-T
• rs1402047607
• NM_001318100.2:c.149C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318100.2(LZTS2):​c.149C>T​(p.Pro50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LZTS2 NM_001318100.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

Genes affected

LZTS2 (HGNC:29381): (leucine zipper tumor suppressor 2) The protein encoded by this gene belongs to the leucine zipper tumor suppressor family of proteins, which function in transcription regulation and cell cycle control. This family member can repress beta-catenin-mediated transcriptional activation and is a negative regulator of the Wnt signaling pathway. It negatively regulates microtubule severing at centrosomes, and is necessary for central spindle formation and cytokinesis completion. It is implicated in cancer, where it may inhibit cell proliferation and decrease susceptibility to tumor development. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07004365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318100.2. 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
	LZTS2	NM_001318100.2	MANE Select	c.149C>T	p.Pro50Leu	missense	Exon 2 of 5	NP_001305029.1	Q9BRK4
	LZTS2	NM_001318099.2		c.149C>T	p.Pro50Leu	missense	Exon 2 of 5	NP_001305028.1	Q9BRK4
	LZTS2	NM_001394950.1		c.149C>T	p.Pro50Leu	missense	Exon 2 of 5	NP_001381879.1	Q9BRK4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	ENST00000454422.2	TSL:2 MANE Select	c.149C>T	p.Pro50Leu	missense	Exon 2 of 5	ENSP00000416972.2	Q9BRK4
	LZTS2	ENST00000370220.1	TSL:1	c.149C>T	p.Pro50Leu	missense	Exon 1 of 4	ENSP00000359240.1	Q9BRK4
	LZTS2	ENST00000370223.7	TSL:1	c.149C>T	p.Pro50Leu	missense	Exon 2 of 5	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247314 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000897

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458386 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725348

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 85914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52554

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

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110348

Other (OTH) AF: 0.00 AC: 0 AN: 60302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.000111 Hom.: 0

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	0.072
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.065
Sift	Benign	0.098	T
Sift4G	Benign	0.58	T
Polyphen		0.018	B
Vest4		0.21
MutPred		0.19		Loss of glycosylation at P50 (P = 0.0304)
MVP		0.22
MPC		0.26
ClinPred		0.13	T
GERP RS		4.0
Varity_R		0.033
gMVP		0.24
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1402047607; hg19: chr10-102762444;