rs807029

Positions:

• chr10-101004290-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.1068+124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,039,366 control chromosomes in the GnomAD database, including 52,884 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 0.36 (11309 hom., cov: 32)
  • Exomes 𝑓: 0.29 (41575 hom.)
• Consequence: LZTS2 NM_001318100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LZTS2	NM_001318100.2	c.1068+124C>T		intron_variant		ENST00000454422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LZTS2	ENST00000454422.2	c.1068+124C>T		intron_variant		2	NM_001318100.2	P1
LZTS2	ENST00000370220.1	c.1068+124C>T		intron_variant		1		P1
LZTS2	ENST00000370223.7	c.1068+124C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55266 AN: 151798 Hom.: 11287 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.294 AC: 261336 AN: 887450 Hom.: 41575 AF XY: 0.295 AC XY: 129680 AN XY: 440230

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.554

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.364 AC: 55334 AN: 151916 Hom.: 11309 Cov.: 32 AF XY: 0.363 AC XY: 26981 AN XY: 74246

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.343

Alfa AF: 0.319 Hom.: 1374

Bravo AF: 0.385

Asia WGS AF: 0.432 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs807029; hg19: chr10-102764047; COSMIC: COSV64653028; COSMIC: COSV64653028;