Genetic Variant LZTS2:p.Arg144His (chr10-101003529-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001318100.2(LZTS2):c.431G>A(p.Arg144His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 1,371,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

LZTS2
NM_001318100.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98

Publications

1 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LZTS2	NM_001318100.2	MANE Select	c.431G>A	p.Arg144His	missense	Exon 3 of 5	NP_001305029.1	Q9BRK4
LZTS2	NM_001318099.2		c.431G>A	p.Arg144His	missense	Exon 3 of 5	NP_001305028.1	Q9BRK4
LZTS2	NM_001394950.1		c.431G>A	p.Arg144His	missense	Exon 3 of 5	NP_001381879.1	Q9BRK4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LZTS2	ENST00000454422.2	TSL:2 MANE Select	c.431G>A	p.Arg144His	missense	Exon 3 of 5	ENSP00000416972.2	Q9BRK4
LZTS2	ENST00000370220.1	TSL:1	c.431G>A	p.Arg144His	missense	Exon 2 of 4	ENSP00000359240.1	Q9BRK4
LZTS2	ENST00000370223.7	TSL:1	c.431G>A	p.Arg144His	missense	Exon 3 of 5	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000549

AC:

AN:

182122

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000292

AC:

AN:

1371010

Hom.:

Cov.:

AF XY:

0.00000447

AC XY:

AN XY:

671794

show subpopulations

African (AFR)

AF:

0.0000327

AC:

AN:

30558

American (AMR)

AF:

0.00

AC:

AN:

30968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20138

East Asian (EAS)

AF:

0.00

AC:

AN:

38896

South Asian (SAS)

AF:

0.00

AC:

AN:

71368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.00000281

AC:

AN:

1067754

Other (OTH)

AF:

0.00

AC:

AN:

56392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.0000238

Hom.:

ExAC

AF:

0.00000844

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.4

PhyloP100

8.0

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.56

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0030

Polyphen

0.98

Vest4

0.90

MVP

0.81

MPC

0.32

ClinPred

0.98

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.58

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over