rs752974

chr10-101002499-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318100.2(LZTS2):c.-40C>T variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,492,776 control chromosomes in the GnomAD database, including 163,078 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (13451 hom., cov: 33)
  • Exomes 𝑓: 0.46 (149627 hom.)
• Consequence: LZTS2 NM_001318100.2 splice_region, 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LZTS2	NM_001318100.2	c.-40C>T		splice_region_variant, 5_prime_UTR_variant	2/5	ENST00000454422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LZTS2	ENST00000454422.2	c.-40C>T		splice_region_variant, 5_prime_UTR_variant	2/5	2	NM_001318100.2	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58295 AN: 152018 Hom.: 13444 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.397

GnomAD3 exomes AF: 0.427 AC: 68891 AN: 161208 Hom.: 16665 AF XY: 0.436 AC XY: 37525 AN XY: 86086

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.510

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.0892

Gnomad SAS exome AF: 0.375

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.463 AC: 620388 AN: 1340640 Hom.: 149627 Cov.: 33 AF XY: 0.462 AC XY: 302160 AN XY: 654630

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.499

Gnomad4 EAS exome AF: 0.0846

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.383 AC: 58304 AN: 152136 Hom.: 13451 Cov.: 33 AF XY: 0.386 AC XY: 28707 AN XY: 74398

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.0957

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.394

Alfa AF: 0.471 Hom.: 17653

Bravo AF: 0.365

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	7.7
Dann	Benign	0.66
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752974; hg19: chr10-102762256; COSMIC: COSV64651312;