10-101002044-C-T

Position:

• chr10-101002044-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000370220(LZTS2):​c.-495C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,856 control chromosomes in the GnomAD database, including 6,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6213 hom., cov: 33)
  • Exomes 𝑓: 0.19 (23 hom.)
• Consequence: LZTS2 ENST00000370220 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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]

LZTS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZTS2	NM_001318100.2	c.-42-453C>T		intron_variant		ENST00000454422.2	NP_001305029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZTS2	ENST00000454422.2	c.-42-453C>T		intron_variant		2	NM_001318100.2	ENSP00000416972.2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40728 AN: 152020 Hom.: 6200 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.194 AC: 139 AN: 718 Hom.: 23 Cov.: 0 AF XY: 0.184 AC XY: 72 AN XY: 392

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.268 AC: 40776 AN: 152138 Hom.: 6213 Cov.: 33 AF XY: 0.270 AC XY: 20098 AN XY: 74370

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.251

Alfa AF: 0.177 Hom.: 601

Bravo AF: 0.285

Asia WGS AF: 0.414 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.94

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

LitVar

Other links and lift over

dbSNP: rs701834; hg19: chr10-102761801; COSMIC: COSV64651760;