10-101002920-A-C

Variant names:

• chr10-101002920-A-C
• NM_001318100.2:c.382A>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_Moderate BP6

The NM_001318100.2(LZTS2):​c.382A>C​(p.Ile128Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.00097 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LZTS2 NM_001318100.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 2.04

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 Likely_benign. Variant got -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.093381554).
• BP6: Variant 10-101002920-A-C is Benign according to our data. Variant chr10-101002920-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206247.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-101002920-A-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS2	NM_001318100.2	c.382A>C	p.Ile128Leu	missense_variant	Exon 2 of 5	ENST00000454422.2	NP_001305029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTS2	ENST00000454422.2	c.382A>C	p.Ile128Leu	missense_variant	Exon 2 of 5	2	NM_001318100.2	ENSP00000416972.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000973 AC: 1412 AN: 1451372 Hom.: 0 Cov.: 32 AF XY: 0.000937 AC XY: 677 AN XY: 722252

Gnomad4 AFR exome AF: 0.000601

Gnomad4 AMR exome AF: 0.0000449

Gnomad4 ASJ exome AF: 0.000193

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.000326

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.000500

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0092	T;T;T;.;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;.;T;D;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.093	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	.;N;.;.;N;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.21	N;N;N;.;N;N
REVEL	Benign	0.11
Sift	Benign	0.33	T;T;T;.;T;T
Sift4G	Benign	0.21	T;T;D;D;T;T
Polyphen		0.041	.;B;.;.;B;.
Vest4		0.41, 0.28
MutPred		0.20		Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);Loss of methylation at K133 (P = 0.0692);
MVP		0.17
MPC		0.25
ClinPred		0.42	T
GERP RS		4.8
Varity_R		0.11
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-102762677;