11-102111105-T-C

Position:

• chr11-102111105-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1 PM2 PP5_Moderate BP4

The NM_001130145.3(YAP1):​c.257T>C​(p.Met86Thr) 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. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YAP1 NM_001130145.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a mutagenesis_site Complete loss of interaction with TEAD1. (size 0) in uniprot entity YAP1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-102111105-T-C is Pathogenic according to our data. Variant chr11-102111105-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1686307.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.2562431). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAP1	NM_001130145.3	c.257T>C	p.Met86Thr	missense_variant	1/9	ENST00000282441.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YAP1	ENST00000282441.10	c.257T>C	p.Met86Thr	missense_variant	1/9	1	NM_001130145.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Uveal coloboma-cleft lip and palate-intellectual disability Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Uncertain	0.65	.;D;.;.;.;.;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.26	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.0	D;D;D;D;.;.;D
REVEL	Benign	0.14
Sift	Benign	0.036	D;D;D;D;.;.;D
Sift4G	Benign	0.36	T;T;T;T;T;T;T
Polyphen		0.097, 0.37, 0.40	.;B;.;.;.;B;B
Vest4		0.36
MutPred		0.35		Gain of glycosylation at M86 (P = 0.0155);Gain of glycosylation at M86 (P = 0.0155);Gain of glycosylation at M86 (P = 0.0155);Gain of glycosylation at M86 (P = 0.0155);Gain of glycosylation at M86 (P = 0.0155);Gain of glycosylation at M86 (P = 0.0155);Gain of glycosylation at M86 (P = 0.0155);
MVP		0.18
MPC		1.5
ClinPred		0.56	D
GERP RS		2.7
Varity_R		0.76
gMVP		0.62

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.

Other links and lift over

hg19: chr11-101981836;