10-101002753-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001318100.2(LZTS2):c.215C>T(p.Pro72Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,168 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
LZTS2
NM_001318100.2 missense
NM_001318100.2 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.25
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.15333378).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTS2 | NM_001318100.2 | c.215C>T | p.Pro72Leu | missense_variant | 2/5 | ENST00000454422.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTS2 | ENST00000454422.2 | c.215C>T | p.Pro72Leu | missense_variant | 2/5 | 2 | NM_001318100.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152194Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000320 AC: 8AN: 249836Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135210
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1460974Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 726820
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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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 submitter | clinical testing | Ambry Genetics | Jun 11, 2024 | The c.215C>T (p.P72L) alteration is located in exon 2 (coding exon 1) of the LZTS2 gene. This alteration results from a C to T substitution at nucleotide position 215, causing the proline (P) at amino acid position 72 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;.;L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;.;D;D
REVEL
Benign
Sift
Benign
D;T;T;.;T;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.74
.;P;.;.;P;.
Vest4
0.35, 0.28
MVP
MPC
0.90
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at