chr10-101007360-C-A

Position:

• chr10-101007360-C-A

Variant summary

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

The NM_001318100.2(LZTS2):​c.*192C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,412,228 control chromosomes in the GnomAD database, including 50,233 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 0.29 (6891 hom., cov: 33)
  • Exomes 𝑓: 0.25 (43342 hom.)
• Consequence: LZTS2 NM_001318100.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LZTS2	NM_001318100.2	c.*192C>A		3_prime_UTR_variant	5/5	ENST00000454422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LZTS2	ENST00000454422.2	c.*192C>A		3_prime_UTR_variant	5/5	2	NM_001318100.2	P1
LZTS2	ENST00000370220.1	c.*192C>A		3_prime_UTR_variant	4/4	1		P1
LZTS2	ENST00000370223.7	c.*192C>A		3_prime_UTR_variant	5/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43819 AN: 152026 Hom.: 6877 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.254 AC: 320452 AN: 1260084 Hom.: 43342 Cov.: 31 AF XY: 0.254 AC XY: 154954 AN XY: 609084

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.557

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.288 AC: 43860 AN: 152144 Hom.: 6891 Cov.: 33 AF XY: 0.290 AC XY: 21557 AN XY: 74386

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.270

Alfa AF: 0.240 Hom.: 7392

Bravo AF: 0.304

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.71
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: rs701836; hg19: chr10-102767117; COSMIC: COSV64652069; COSMIC: COSV64652069;