Variant 10-101003609-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001318100.2(LZTS2):c.511G>A(p.Gly171Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000223 in 1,598,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

LZTS2
NM_001318100.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3127805).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS2	NM_001318100.2 link	c.511G>A	p.Gly171Arg	missense_variant	Exon 3 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.511G>A	p.Gly171Arg	missense_variant	Exon 3 of 5	2	NM_001318100.2	ENSP00000416972.2		Q9BRK4B1AL12

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000914

AC:

AN:

240658

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

129410

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000239

AC:

345

AN:

1446172

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

172

AN XY:

717288

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000358

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000177

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000989

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511G>A (p.G171R) alteration is located in exon 3 (coding exon 2) of the LZTS2 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the glycine (G) at amino acid position 171 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

T;T;T;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;.;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.31

T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.9

.;L;.;L;.

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-4.5

D;D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.020

D;D;D;D;D

Polyphen

1.0

.;D;.;D;.

Vest4

0.64, 0.64

MutPred

0.36

Gain of methylation at G171 (P = 0.0075);Gain of methylation at G171 (P = 0.0075);Gain of methylation at G171 (P = 0.0075);Gain of methylation at G171 (P = 0.0075);Gain of methylation at G171 (P = 0.0075);

MVP

0.23

MPC

0.94

ClinPred

0.45

GERP RS

5.3

Varity_R

0.27

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over