Genetic Variant ENST00000370220.1:c.-495C>T (chr10-101002044-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000370220.1(LZTS2):c.-495C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,856 control chromosomes in the GnomAD database, including 6,236 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 0.27 ( 6213 hom., cov: 33)

Exomes 𝑓: 0.19 ( 23 hom. )

Consequence

LZTS2
ENST00000370220.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

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: ENST00000370220.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LZTS2	NM_001318100.2	MANE Select	c.-42-453C>T	intron	N/A	NP_001305029.1	Q9BRK4
LZTS2	NM_001318099.2		c.-42-453C>T	intron	N/A	NP_001305028.1	Q9BRK4
LZTS2	NM_001394950.1		c.-42-453C>T	intron	N/A	NP_001381879.1	Q9BRK4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LZTS2	ENST00000370220.1	TSL:1	c.-495C>T	5_prime_UTR	Exon 1 of 4	ENSP00000359240.1	Q9BRK4
LZTS2	ENST00000454422.2	TSL:2 MANE Select	c.-42-453C>T	intron	N/A	ENSP00000416972.2	Q9BRK4
LZTS2	ENST00000370223.7	TSL:1	c.-42-453C>T	intron	N/A	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40728

AN:

152020

Hom.:

6200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.194

AC:

139

AN:

718

Hom.:

Cov.:

AF XY:

0.184

AC XY:

AN XY:

392

show subpopulations

African (AFR)

AF:

0.458

AC:

AN:

American (AMR)

AF:

0.111

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.444

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.0217

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.175

AC:

AN:

536

Other (OTH)

AF:

0.267

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.268

AC:

40776

AN:

152138

Hom.:

6213

Cov.:

AF XY:

0.270

AC XY:

20098

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.368

AC:

15261

AN:

41480

American (AMR)

AF:

0.297

AC:

4539

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

517

AN:

3472

East Asian (EAS)

AF:

0.547

AC:

2829

AN:

5168

South Asian (SAS)

AF:

0.304

AC:

1470

AN:

4830

European-Finnish (FIN)

AF:

0.173

AC:

1837

AN:

10590

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13605

AN:

67982

Other (OTH)

AF:

0.251

AC:

529

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1507

3014

4522

6029

7536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.183

Hom.:

659

Bravo

AF:

0.285

Asia WGS

AF:

0.414

AC:

1438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

-0.090

Mutation Taster

=299/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over