Genetic Variant LZTS2:c.*230C>G (chr10-101007398-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.245

Variant links:

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]

LZTS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS2	NM_001318100.2 link	c.*230C>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000454422.2	NP_001305029.1	Q9BRK4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LZTS2	ENST00000454422.2 link	c.*230C>G	3_prime_UTR_variant	Exon 5 of 5	2	NM_001318100.2	ENSP00000416972.2	Q9BRK4B1AL12
LZTS2	ENST00000370220.1 link	c.*230C>G	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000359240.1	Q9BRK4
LZTS2	ENST00000370223.7 link	c.*230C>G	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42880

AN:

152066

Hom.:

6568

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.303

AC:

17884

AN:

58980

Hom.:

3076

AF XY:

0.300

AC XY:

9227

AN XY:

30726

show subpopulations

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 SAS exome

AF:

0.295

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.:

AF XY:

0.255

AC XY:

157049

AN XY:

616668

show subpopulations

Gnomad4 AFR exome

AF:

0.361

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.559

Gnomad4 SAS exome

AF:

0.291

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.282

AC:

42921

AN:

152184

Hom.:

6580

Cov.:

AF XY:

0.283

AC XY:

21078

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.548

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.265

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.5

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over