dbSNP rs701836: 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

Publications

19 publications found

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:

Genome browser will be placed here

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

African (AFR)

AF:

0.385

AC:

10465

AN:

27174

American (AMR)

AF:

0.349

AC:

6232

AN:

17846

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

3451

AN:

18478

East Asian (EAS)

AF:

0.557

AC:

18118

AN:

32500

South Asian (SAS)

AF:

0.290

AC:

17074

AN:

58834

European-Finnish (FIN)

AF:

0.208

AC:

6232

AN:

29898

Middle Eastern (MID)

AF:

0.226

AC:

974

AN:

4304

European-Non Finnish (NFE)

AF:

0.239

AC:

243934

AN:

1018688

Other (OTH)

AF:

0.267

AC:

13972

AN:

52362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

12376

24751

37127

49502

61878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.366

AC:

15205

AN:

41488

American (AMR)

AF:

0.312

AC:

4774

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3472

East Asian (EAS)

AF:

0.547

AC:

2831

AN:

5174

South Asian (SAS)

AF:

0.306

AC:

1480

AN:

4830

European-Finnish (FIN)

AF:

0.200

AC:

2119

AN:

10604

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.235

AC:

15949

AN:

67962

Other (OTH)

AF:

0.270

AC:

571

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1590

3180

4770

6360

7950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

(source)

DANN

Benign

0.71

PhyloP100

0.029

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over