chr10-101002684-G-A

Position:

• chr10-101002684-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318100.2(LZTS2):​c.146G>A​(p.Gly49Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,176 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LZTS2 NM_001318100.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13544318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZTS2	NM_001318100.2	c.146G>A	p.Gly49Asp	missense_variant	2/5	ENST00000454422.2	NP_001305029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZTS2	ENST00000454422.2	c.146G>A	p.Gly49Asp	missense_variant	2/5	2	NM_001318100.2	ENSP00000416972.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457176 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724638

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.146G>A (p.G49D) alteration is located in exon 2 (coding exon 1) of the LZTS2 gene. This alteration results from a G to A substitution at nucleotide position 146, causing the glycine (G) at amino acid position 49 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	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;T;T;.;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.75	T;.;T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;.;.;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N;N;N;.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0090	D;T;T;.;T;D
Sift4G	Benign	0.14	T;T;T;T;T;T
Polyphen		0.84	.;P;.;.;P;.
Vest4		0.31, 0.25
MutPred		0.10		Loss of glycosylation at P51 (P = 0.0712);Loss of glycosylation at P51 (P = 0.0712);Loss of glycosylation at P51 (P = 0.0712);Loss of glycosylation at P51 (P = 0.0712);Loss of glycosylation at P51 (P = 0.0712);Loss of glycosylation at P51 (P = 0.0712);
MVP		0.34
MPC		0.47
ClinPred		0.46	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-102762441;