13-20975169-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014572.3(LATS2):​c.2968G>A​(p.Val990Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LATS2
NM_014572.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08080283).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LATS2NM_014572.3 linkc.2968G>A p.Val990Ile missense_variant Exon 8 of 8 ENST00000382592.5 NP_055387.2 Q9NRM7A0A024RDM3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LATS2ENST00000382592.5 linkc.2968G>A p.Val990Ile missense_variant Exon 8 of 8 1 NM_014572.3 ENSP00000372035.4 Q9NRM7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 13, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2968G>A (p.V990I) alteration is located in exon 8 (coding exon 7) of the LATS2 gene. This alteration results from a G to A substitution at nucleotide position 2968, causing the valine (V) at amino acid position 990 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
16
DANN
Benign
0.53
DEOGEN2
Benign
0.065
T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.17
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.12
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.22
N
REVEL
Benign
0.044
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.010
B
Vest4
0.14
MutPred
0.27
Gain of catalytic residue at A987 (P = 0.0111);
MVP
0.26
MPC
0.48
ClinPred
0.34
T
GERP RS
4.2
Varity_R
0.022
gMVP
0.29

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.

Other links and lift over

dbSNP: rs1869542128; hg19: chr13-21549308; API