Variant 10-101002920-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_001318100.2(LZTS2):c.382A>C(p.Ile128Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.00097 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LZTS2
NM_001318100.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 2.04

Variant links:

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]

LZTS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.093381554).

BP6

Variant 10-101002920-A-C is Benign according to our data. Variant chr10-101002920-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206247.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-101002920-A-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS2	NM_001318100.2 link	c.382A>C	p.Ile128Leu	missense_variant	Exon 2 of 5	ENST00000454422.2	NP_001305029.1	Q9BRK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTS2	ENST00000454422.2 link	c.382A>C	p.Ile128Leu	missense_variant	Exon 2 of 5	2	NM_001318100.2	ENSP00000416972.2		Q9BRK4B1AL12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000973

AC:

1412

AN:

1451372

Hom.:

Cov.:

AF XY:

0.000937

AC XY:

677

AN XY:

722252

show subpopulations

Gnomad4 AFR exome

AF:

0.000601

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.000193

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000326

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.000500

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0092

T;T;T;.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

T;.;T;D;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.093

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

.;N;.;.;N;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.21

N;N;N;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.33

T;T;T;.;T;T

Sift4G

Benign

0.21

T;T;D;D;T;T

Polyphen

0.041

.;B;.;.;B;.

Vest4

0.41, 0.28

MutPred

0.20

Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);

MVP

0.17

MPC

0.25

ClinPred

0.42

GERP RS

4.8

Varity_R

0.11

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over