rs752974

Variant names:

• chr10-101002499-C-T
• rs752974
• NM_001318100.2:c.-40C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318100.2(LZTS2):​c.-40C>T variant causes a 5 prime UTR premature start codon gain 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. 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 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LZTS2	NM_001318100.2	c.-40C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	ENST00000454422.2	NP_001305029.1
LZTS2	NM_001318100.2	c.-40C>T		splice_region_variant	Exon 2 of 5	ENST00000454422.2	NP_001305029.1
LZTS2	NM_001318100.2	c.-40C>T		5_prime_UTR_variant	Exon 2 of 5	ENST00000454422.2	NP_001305029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTS2	ENST00000454422.2	c.-40C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	2	NM_001318100.2	ENSP00000416972.2
LZTS2	ENST00000454422.2	c.-40C>T		splice_region_variant	Exon 2 of 5	2	NM_001318100.2	ENSP00000416972.2
LZTS2	ENST00000454422.2	c.-40C>T		5_prime_UTR_variant	Exon 2 of 5	2	NM_001318100.2	ENSP00000416972.2

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

GnomAD2 exomes AF: 0.427 AC: 68891 AN: 161208 AF XY: 0.436

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 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

African (AFR) AF: 0.120 AC: 3540 AN: 29508

American (AMR) AF: 0.499 AC: 13245 AN: 26564

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 9731 AN: 19506

East Asian (EAS) AF: 0.0846 AC: 3154 AN: 37266

South Asian (SAS) AF: 0.386 AC: 25753 AN: 66664

European-Finnish (FIN) AF: 0.556 AC: 26791 AN: 48160

Middle Eastern (MID) AF: 0.467 AC: 2215 AN: 4740

European-Non Finnish (NFE) AF: 0.486 AC: 512191 AN: 1053158

Other (OTH) AF: 0.432 AC: 23768 AN: 55074

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

African (AFR) AF: 0.141 AC: 5857 AN: 41502

American (AMR) AF: 0.470 AC: 7192 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1705 AN: 3472

East Asian (EAS) AF: 0.0957 AC: 495 AN: 5170

South Asian (SAS) AF: 0.377 AC: 1820 AN: 4822

European-Finnish (FIN) AF: 0.552 AC: 5848 AN: 10590

Middle Eastern (MID) AF: 0.552 AC: 160 AN: 290

European-Non Finnish (NFE) AF: 0.498 AC: 33862 AN: 67972

Other (OTH) AF: 0.394 AC: 833 AN: 2114

Alfa AF: 0.458 Hom.: 21994

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
PhyloP100		1.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Mutation Taster		=297/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs752974; hg19: chr10-102762256; COSMIC: COSV64651312;