rs41291476

Positions:

• chr10-101002787-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001318100.2(LZTS2):​c.249C>T​(p.Val83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,613,766 control chromosomes in the GnomAD database, including 5 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 0.0014 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: LZTS2 NM_001318100.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.394 with no splicing effect.
• BS2: High AC in GnomAd4 at 218 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZTS2	NM_001318100.2	c.249C>T	p.Val83=	synonymous_variant	2/5	ENST00000454422.2	NP_001305029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZTS2	ENST00000454422.2	c.249C>T	p.Val83=	synonymous_variant	2/5	2	NM_001318100.2	ENSP00000416972	P1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 218 AN: 152240 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00144 AC: 362 AN: 250720 Hom.: 1 AF XY: 0.00149 AC XY: 202 AN XY: 135584

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.00345

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00185

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00170 AC: 2478 AN: 1461408 Hom.: 3 Cov.: 32 AF XY: 0.00165 AC XY: 1202 AN XY: 727014

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.000957

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.00195

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00143 AC: 218 AN: 152358 Hom.: 2 Cov.: 33 AF XY: 0.00140 AC XY: 104 AN XY: 74504

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00192 Hom.: 0

Bravo AF: 0.00189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.8
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs41291476; hg19: chr10-102762544;