chr10-101003515-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001318100.2(LZTS2):ā€‹c.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

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15
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]

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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
LZTS2NM_001318100.2 linkuse as main transcriptc.417G>C p.Glu139Asp missense_variant 3/5 ENST00000454422.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LZTS2ENST00000454422.2 linkuse as main transcriptc.417G>C p.Glu139Asp missense_variant 3/52 NM_001318100.2 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000561
AC:
1
AN:
178290
Hom.:
0
AF XY:
0.0000107
AC XY:
1
AN XY:
93592
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:
0.0000116
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.33e-7
AC:
1
AN:
1364046
Hom.:
0
Cov.:
31
AF XY:
0.00000150
AC XY:
1
AN XY:
667314
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.40e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 GeneticsJul 13, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.064
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.079
T;T;T;T;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.82
T;.;D;D;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.28
T;T;T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.1
.;M;.;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.9
N;N;N;N;N
REVEL
Benign
0.088
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Uncertain
0.042
D;T;D;T;D
Polyphen
1.0
.;D;.;D;.
Vest4
0.39, 0.40
MutPred
0.22
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
0.36
MPC
0.74
ClinPred
0.86
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.35
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs1160371130; hg19: chr10-102763272; API