Variant chr11-102110934-C-A 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.86C>A(p.Pro29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

YAP1
NM_001130145.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.283

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=0.22888145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAP1	NM_001130145.3 linkuse as main transcript	c.86C>A	p.Pro29Gln	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.86C>A	p.Pro29Gln	missense_variant	1/9	1	NM_001130145.3	P2	P46937-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1316206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648196

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.86C>A (p.P29Q) alteration is located in exon 1 (coding exon 1) of the YAP1 gene. This alteration results from a C to A substitution at nucleotide position 86, causing the proline (P) at amino acid position 29 to be replaced by a glutamine (Q). 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

0.058

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.13

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

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.60

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

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.23

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

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.4

L;L;L;L;L;L;L

MutationTaster

Benign

0.73

D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.37

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

REVEL

Benign

0.070

Sift

Benign

0.34

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

Sift4G

Benign

0.25

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

Polyphen

0.91, 0.94

.;P;.;.;.;P;P

Vest4

0.14

MutPred

0.25

Loss of catalytic residue at P29 (P = 0.0125);Loss of catalytic residue at P29 (P = 0.0125);Loss of catalytic residue at P29 (P = 0.0125);Loss of catalytic residue at P29 (P = 0.0125);Loss of catalytic residue at P29 (P = 0.0125);Loss of catalytic residue at P29 (P = 0.0125);Loss of catalytic residue at P29 (P = 0.0125);

MVP

0.082

MPC

1.1

ClinPred

0.46

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.060

gMVP

0.13

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over