10-101007398-C-G

Variant names:

• chr10-101007398-C-G
• rs14177
• NM_001318100.2:c.*230C>G

Variant summary

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

The NM_001318100.2(LZTS2):​c.*230C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,422,692 control chromosomes in the GnomAD database, including 50,346 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 0.28 (6580 hom., cov: 33)
  • Exomes 𝑓: 0.25 (43766 hom.)
• Consequence: LZTS2 NM_001318100.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 8 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	NM_001318100.2	MANE Select	c.*230C>G		3_prime_UTR	Exon 5 of 5	NP_001305029.1	Q9BRK4
	LZTS2	NM_001318099.2		c.*230C>G		3_prime_UTR	Exon 5 of 5	NP_001305028.1	Q9BRK4
	LZTS2	NM_001394950.1		c.*230C>G		3_prime_UTR	Exon 5 of 5	NP_001381879.1	Q9BRK4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	ENST00000454422.2	TSL:2 MANE Select	c.*230C>G		3_prime_UTR	Exon 5 of 5	ENSP00000416972.2	Q9BRK4
	LZTS2	ENST00000370220.1	TSL:1	c.*230C>G		3_prime_UTR	Exon 4 of 4	ENSP00000359240.1	Q9BRK4
	LZTS2	ENST00000370223.7	TSL:1	c.*230C>G		3_prime_UTR	Exon 5 of 5	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42880 AN: 152066 Hom.: 6568 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.303 AC: 17884 AN: 58980 AF XY: 0.300

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.254 AC: 323329 AN: 1270508 Hom.: 43766 Cov.: 31 AF XY: 0.255 AC XY: 157049 AN XY: 616668

African (AFR) AF: 0.361 AC: 9848 AN: 27290

American (AMR) AF: 0.357 AC: 7207 AN: 20164

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 3638 AN: 19316

East Asian (EAS) AF: 0.559 AC: 17770 AN: 31788

South Asian (SAS) AF: 0.291 AC: 17955 AN: 61752

European-Finnish (FIN) AF: 0.210 AC: 6316 AN: 30112

Middle Eastern (MID) AF: 0.223 AC: 1154 AN: 5170

European-Non Finnish (NFE) AF: 0.240 AC: 245410 AN: 1022168

Other (OTH) AF: 0.266 AC: 14031 AN: 52748

GnomAD4 genome AF: 0.282 AC: 42921 AN: 152184 Hom.: 6580 Cov.: 33 AF XY: 0.283 AC XY: 21078 AN XY: 74394

African (AFR) AF: 0.343 AC: 14234 AN: 41518

American (AMR) AF: 0.309 AC: 4726 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2830 AN: 5168

South Asian (SAS) AF: 0.305 AC: 1475 AN: 4830

European-Finnish (FIN) AF: 0.200 AC: 2120 AN: 10604

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16044 AN: 67988

Other (OTH) AF: 0.265 AC: 559 AN: 2110

Alfa AF: 0.172 Hom.: 525

Bravo AF: 0.297

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		0.24
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: rs14177; hg19: chr10-102767155;