11-102226584-T-C

Variant names:

• chr11-102226584-T-C
• rs2282652
• NM_001130145.3:c.1164-885T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130145.3(YAP1):​c.1164-885T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,014 control chromosomes in the GnomAD database, including 7,248 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7248 hom., cov: 32)
• Consequence: YAP1 NM_001130145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• uveal coloboma-cleft lip and palate-intellectual disability

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAP1	NM_001130145.3	c.1164-885T>C		intron_variant	Intron 7 of 8	ENST00000282441.10	NP_001123617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAP1	ENST00000282441.10	c.1164-885T>C		intron_variant	Intron 7 of 8	1	NM_001130145.3	ENSP00000282441.5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46262 AN: 151896 Hom.: 7242 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 46301 AN: 152014 Hom.: 7248 Cov.: 32 AF XY: 0.305 AC XY: 22680 AN XY: 74300

African (AFR) AF: 0.238 AC: 9889 AN: 41470

American (AMR) AF: 0.310 AC: 4733 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1868 AN: 5160

South Asian (SAS) AF: 0.292 AC: 1412 AN: 4828

European-Finnish (FIN) AF: 0.341 AC: 3599 AN: 10548

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22632 AN: 67950

Other (OTH) AF: 0.328 AC: 691 AN: 2108

Alfa AF: 0.325 Hom.: 6755

Bravo AF: 0.303

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.90
DANN	Benign	0.48
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs2282652; hg19: chr11-102097315;