NM_014572.3:c.2846C>A

Variant names:

• chr13-20975291-G-T
• rs1201048392
• NM_014572.3:c.2846C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014572.3(LATS2):​c.2846C>A​(p.Thr949Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T949I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LATS2 NM_014572.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37922123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LATS2	NM_014572.3	c.2846C>A	p.Thr949Asn	missense_variant	Exon 8 of 8	ENST00000382592.5	NP_055387.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LATS2	ENST00000382592.5	c.2846C>A	p.Thr949Asn	missense_variant	Exon 8 of 8	1	NM_014572.3	ENSP00000372035.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.70
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.14	N
PhyloP100		4.3
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Benign	0.51	T
Sift4G	Benign	0.41	T
Polyphen		0.77	P
Vest4		0.43
MutPred		0.45		Gain of catalytic residue at S954 (P = 0);
MVP		0.64
MPC		1.1
ClinPred		0.41	T
GERP RS		3.3
Varity_R		0.064
gMVP		0.74
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs1201048392; hg19: chr13-21549430;