chr10-101003515-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001318100.2(LZTS2):āc.417G>Cā(p.Glu139Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000733 in 1,364,046 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 (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 7.3e-7 ( 0 hom. )
Consequence
LZTS2
NM_001318100.2 missense
NM_001318100.2 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 4.15
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2812768).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTS2 | NM_001318100.2 | c.417G>C | p.Glu139Asp | missense_variant | 3/5 | ENST00000454422.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTS2 | ENST00000454422.2 | c.417G>C | p.Glu139Asp | missense_variant | 3/5 | 2 | NM_001318100.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000561 AC: 1AN: 178290Hom.: 0 AF XY: 0.0000107 AC XY: 1AN XY: 93592
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GnomAD4 exome AF: 7.33e-7 AC: 1AN: 1364046Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1AN XY: 667314
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GnomAD4 genome Cov.: 33
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33
Bravo
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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 | Jul 13, 2022 | The c.417G>C (p.E139D) alteration is located in exon 3 (coding exon 2) of the LZTS2 gene. This alteration results from a G to C substitution at nucleotide position 417, causing the glutamic acid (E) at amino acid position 139 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D
Sift4G
Uncertain
D;T;D;T;D
Polyphen
1.0
.;D;.;D;.
Vest4
0.39, 0.40
MutPred
Gain of MoRF binding (P = 0.1117);Gain of MoRF binding (P = 0.1117);Gain of MoRF binding (P = 0.1117);Gain of MoRF binding (P = 0.1117);Gain of MoRF binding (P = 0.1117);
MVP
MPC
0.74
ClinPred
D
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