chr10-101002566-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001318100.2(LZTS2):ā€‹c.28C>Gā€‹(p.Pro10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,534,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000024 ( 0 hom. )

Consequence

LZTS2
NM_001318100.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.774
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.097460985).
BS2
High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LZTS2NM_001318100.2 linkuse as main transcriptc.28C>G p.Pro10Ala missense_variant 2/5 ENST00000454422.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LZTS2ENST00000454422.2 linkuse as main transcriptc.28C>G p.Pro10Ala missense_variant 2/52 NM_001318100.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000106
AC:
2
AN:
188598
Hom.:
0
AF XY:
0.00000997
AC XY:
1
AN XY:
100252
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000225
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000239
AC:
33
AN:
1381820
Hom.:
0
Cov.:
32
AF XY:
0.0000236
AC XY:
16
AN XY:
678598
show subpopulations
Gnomad4 AFR exome
AF:
0.0000646
Gnomad4 AMR exome
AF:
0.00
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:
0.0000261
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 19, 2023The c.28C>G (p.P10A) alteration is located in exon 2 (coding exon 1) of the LZTS2 gene. This alteration results from a C to G substitution at nucleotide position 28, causing the proline (P) at amino acid position 10 to be replaced by an alanine (A). 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
0.074
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.030
T;T;T;.;T;.
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.82
T;.;T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.097
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
.;L;.;.;L;.
MutationTaster
Benign
0.95
D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.2
N;N;N;.;N;N
REVEL
Benign
0.083
Sift
Benign
0.16
T;D;T;.;D;T
Sift4G
Benign
0.28
T;T;T;T;T;T
Polyphen
0.0
.;B;.;.;B;.
Vest4
0.24, 0.19
MutPred
0.17
Loss of glycosylation at P10 (P = 0.0344);Loss of glycosylation at P10 (P = 0.0344);Loss of glycosylation at P10 (P = 0.0344);Loss of glycosylation at P10 (P = 0.0344);Loss of glycosylation at P10 (P = 0.0344);Loss of glycosylation at P10 (P = 0.0344);
MVP
0.10
MPC
0.25
ClinPred
0.11
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.079
gMVP
0.24

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.

Other links and lift over

dbSNP: rs756673185; hg19: chr10-102762323; API