Variant 10-101003771-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001318100.2(LZTS2):c.673C>G(p.Leu225Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000924 in 1,613,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

LZTS2
NM_001318100.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.337

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034448564).

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS2	NM_001318100.2 link	c.673C>G	p.Leu225Val	missense_variant	Exon 3 of 5	ENST00000454422.2	NP_001305029.1	Q9BRK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LZTS2	ENST00000454422.2 link	c.673C>G	p.Leu225Val	missense_variant	Exon 3 of 5	2	NM_001318100.2	ENSP00000416972.2	Q9BRK4B1AL12
LZTS2	ENST00000370220.1 link	c.673C>G	p.Leu225Val	missense_variant	Exon 2 of 4	1		ENSP00000359240.1	Q9BRK4
LZTS2	ENST00000370223.7 link	c.673C>G	p.Leu225Val	missense_variant	Exon 3 of 5	1		ENSP00000359243.3	Q9BRK4
LZTS2	ENST00000426584.5 link	c.673C>G	p.Leu225Val	missense_variant	Exon 3 of 3	3		ENSP00000407713.1	B1AL13

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

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:

0.000214

AC:

AN:

248038

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000722

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000698

AC:

102

AN:

1460788

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000308

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00255

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:

0.0000564

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.673C>G (p.L225V) alteration is located in exon 3 (coding exon 2) of the LZTS2 gene. This alteration results from a C to G substitution at nucleotide position 673, causing the leucine (L) at amino acid position 225 to be replaced by a valine (V). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.88

D;.;D

M_CAP

Benign

0.062

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.7

.;M;M

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.55, 0.55

MVP

0.56

MPC

0.87

ClinPred

0.13

GERP RS

-1.3

Varity_R

0.21

gMVP

0.69

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