rs807029

Variant names:

• chr10-101004290-C-T
• rs807029
• NM_001318100.2:c.1068+124C>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.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
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318100.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	NM_001318100.2	MANE Select	c.1068+124C>T		intron	N/A	NP_001305029.1
	LZTS2	NM_001318099.2		c.1068+124C>T		intron	N/A	NP_001305028.1
	LZTS2	NM_001394950.1		c.1068+124C>T		intron	N/A	NP_001381879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	ENST00000454422.2	TSL:2 MANE Select	c.1068+124C>T		intron	N/A	ENSP00000416972.2
	LZTS2	ENST00000370220.1	TSL:1	c.1068+124C>T		intron	N/A	ENSP00000359240.1
	LZTS2	ENST00000370223.7	TSL:1	c.1068+124C>T		intron	N/A	ENSP00000359243.3

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

African (AFR) AF: 0.553 AC: 11297 AN: 20438

American (AMR) AF: 0.398 AC: 7379 AN: 18534

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 3775 AN: 16146

East Asian (EAS) AF: 0.554 AC: 17969 AN: 32426

South Asian (SAS) AF: 0.328 AC: 16789 AN: 51116

European-Finnish (FIN) AF: 0.232 AC: 7804 AN: 33642

Middle Eastern (MID) AF: 0.266 AC: 859 AN: 3228

European-Non Finnish (NFE) AF: 0.272 AC: 183119 AN: 672076

Other (OTH) AF: 0.310 AC: 12345 AN: 39844

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

African (AFR) AF: 0.543 AC: 22461 AN: 41402

American (AMR) AF: 0.364 AC: 5554 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2802 AN: 5164

South Asian (SAS) AF: 0.341 AC: 1636 AN: 4802

European-Finnish (FIN) AF: 0.225 AC: 2374 AN: 10568

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18674 AN: 67926

Other (OTH) AF: 0.343 AC: 721 AN: 2102

Alfa AF: 0.332 Hom.: 1755

Bravo AF: 0.385

Asia WGS AF: 0.432 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.63
PhyloP100		-0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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