Variant 13-20975100-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014572.3(LATS2):c.3037G>A(p.Asp1013Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,614,182 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 13 hom. )

Consequence

LATS2
NM_014572.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

LATS2 (HGNC:6515): (large tumor suppressor kinase 2) This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family. The protein localizes to centrosomes during interphase, and early and late metaphase. It interacts with the centrosomal proteins aurora-A and ajuba and is required for accumulation of gamma-tubulin and spindle formation at the onset of mitosis. It also interacts with a negative regulator of p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a co-repressor of androgen-responsive gene expression. [provided by RefSeq, Jul 2008]

LATS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034824014).

BP6

Variant 13-20975100-C-T is Benign according to our data. Variant chr13-20975100-C-T is described in ClinVar as [Benign]. Clinvar id is 722404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00584 (889/152290) while in subpopulation AFR AF= 0.0203 (843/41548). AF 95% confidence interval is 0.0192. There are 10 homozygotes in gnomad4. There are 434 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 889 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LATS2	NM_014572.3 linkuse as main transcript	c.3037G>A	p.Asp1013Asn	missense_variant	8/8	ENST00000382592.5	NP_055387.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LATS2	ENST00000382592.5 linkuse as main transcript	c.3037G>A	p.Asp1013Asn	missense_variant	8/8	1	NM_014572.3	ENSP00000372035	P1

Frequencies

GnomAD3 genomes

AF:

0.00584

AC:

888

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00134

AC:

337

AN:

251488

Hom.:

AF XY:

0.000986

AC XY:

134

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0194

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000586

AC:

857

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000476

AC XY:

346

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0216

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00584

AC:

889

AN:

152290

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

434

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0203

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000986

Hom.:

Bravo

AF:

0.00617

ESP6500AA

AF:

0.0193

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00167

AC:

203

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

REVEL

Benign

0.13

Sift

Benign

0.092

Sift4G

Uncertain

0.017

Polyphen

0.015

Vest4

0.026

MVP

0.75

MPC

0.58

ClinPred

0.021

GERP RS

3.5

Varity_R

0.070

gMVP

0.47

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over