Variant 11-102111011-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001130145.3(YAP1):c.163G>T(p.Val55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.9e-7 ( 0 hom. )

Consequence

YAP1
NM_001130145.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.711

Variant links:

Genes affected

YAP1 (HGNC:16262): (Yes1 associated transcriptional regulator) This gene encodes a downstream nuclear effector of the Hippo signaling pathway which is involved in development, growth, repair, and homeostasis. This gene is known to play a role in the development and progression of multiple cancers as a transcriptional regulator of this signaling pathway and may function as a potential target for cancer treatment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2013]

YAP1 links:

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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=0.15738308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAP1	NM_001130145.3 linkuse as main transcript	c.163G>T	p.Val55Leu	missense_variant	1/9	ENST00000282441.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YAP1	ENST00000282441.10 linkuse as main transcript	c.163G>T	p.Val55Leu	missense_variant	1/9	1	NM_001130145.3	P2	P46937-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719162

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Uveal coloboma-cleft lip and palate-intellectual disability

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Oct 29, 2018

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,BP1. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.28

.;T;.;.;.;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.81

T;T;T;T;T;T;T

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.16

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.52

N;N;N;N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.4

N;N;N;N;.;.;N

REVEL

Benign

0.035

Sift

Benign

0.091

T;T;T;D;.;.;T

Sift4G

Benign

0.19

T;T;T;T;T;T;T

Polyphen

0.0060, 0.044, 0.048

.;B;.;.;.;B;B

Vest4

0.063

MutPred

0.27

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.18

MPC

1.2

ClinPred

0.27

GERP RS

2.4

Varity_R

0.46

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.

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