Genetic Variant LZTS2:c.*192C>A (chr10-101007360-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001318100.2(LZTS2):c.*192C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,412,228 control chromosomes in the GnomAD database, including 50,233 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 0.29 ( 6891 hom., cov: 33)

Exomes 𝑓: 0.25 ( 43342 hom. )

Consequence

LZTS2
NM_001318100.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS2	NM_001318100.2 link	c.*192C>A		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.*192C>A	3_prime_UTR_variant	Exon 5 of 5	2	NM_001318100.2	ENSP00000416972.2	Q9BRK4B1AL12
LZTS2	ENST00000370220.1 link	c.*192C>A	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000359240.1	Q9BRK4
LZTS2	ENST00000370223.7 link	c.*192C>A	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43819

AN:

152026

Hom.:

6877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.268

GnomAD4 exome

AF:

0.254

AC:

320452

AN:

1260084

Hom.:

43342

Cov.:

AF XY:

0.254

AC XY:

154954

AN XY:

609084

show subpopulations

Gnomad4 AFR exome

AF:

0.385

AC:

10465

AN:

27174

Gnomad4 AMR exome

AF:

0.349

AC:

6232

AN:

17846

Gnomad4 ASJ exome

AF:

0.187

AC:

3451

AN:

18478

Gnomad4 EAS exome

AF:

0.557

AC:

18118

AN:

32500

Gnomad4 SAS exome

AF:

0.290

AC:

17074

AN:

58834

Gnomad4 FIN exome

AF:

0.208

AC:

6232

AN:

29898

Gnomad4 NFE exome

AF:

0.239

AC:

243934

AN:

1018688

Gnomad4 Remaining exome

AF:

0.267

AC:

13972

AN:

52362

Heterozygous variant carriers

12376

24751

37127

49502

61878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

9040

18080

27120

36160

45200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.288

AC:

43860

AN:

152144

Hom.:

6891

Cov.:

AF XY:

0.290

AC XY:

21557

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.366

AC:

0.366492

AN:

0.366492

Gnomad4 AMR

AF:

0.312

AC:

0.312149

AN:

0.312149

Gnomad4 ASJ

AF:

0.197

AC:

0.196717

AN:

0.196717

Gnomad4 EAS

AF:

0.547

AC:

0.547159

AN:

0.547159

Gnomad4 SAS

AF:

0.306

AC:

0.306418

AN:

0.306418

Gnomad4 FIN

AF:

0.200

AC:

0.19983

AN:

0.19983

Gnomad4 NFE

AF:

0.235

AC:

0.234675

AN:

0.234675

Gnomad4 OTH

AF:

0.270

AC:

0.270104

AN:

0.270104

Heterozygous variant carriers

1590

3180

4770

6360

7950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.254

Hom.:

14352

Bravo

AF:

0.304

Asia WGS

AF:

0.406

AC:

1413

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

DANN

Benign

0.71

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

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