Variant 13-20981461-T-C 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 ENST00000382592.5(LATS2):c.2665+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,612,078 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 21 hom. )

Consequence

LATS2
ENST00000382592.5 splice_region, intron

Scores

Splicing: ADA: 0.0005560

Clinical Significance

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

Conservation

PhyloP100: 0.463

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 13-20981461-T-C is Benign according to our data. Variant chr13-20981461-T-C is described in ClinVar as [Benign]. Clinvar id is 784478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00131 (1919/1459752) while in subpopulation AMR AF= 0.0236 (1051/44538). AF 95% confidence interval is 0.0224. There are 21 homozygotes in gnomad4_exome. There are 825 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 389 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LATS2	NM_014572.3 linkuse as main transcript	c.2665+5A>G		splice_region_variant, intron_variant		ENST00000382592.5	NP_055387.2	Q9NRM7A0A024RDM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LATS2	ENST00000382592.5 linkuse as main transcript	c.2665+5A>G		splice_region_variant, intron_variant		1	NM_014572.3	ENSP00000372035.4		Q9NRM7

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00479

AC:

1194

AN:

249174

Hom.:

AF XY:

0.00373

AC XY:

502

AN XY:

134648

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0149

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.0000931

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.00131

AC:

1919

AN:

1459752

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

825

AN XY:

726096

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.0000810

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00255

AC:

389

AN:

152326

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

212

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.0153

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0155

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.000675

Hom.:

Bravo

AF:

0.00461

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

8.0

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00056

dbscSNV1_RF

Benign

0.034

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