11-102110955-C-CGGCACCCGCGGCGACCCAGGCGGCGCCGCA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_001130145.3(YAP1):c.115_144dup(p.Ala39_Pro48dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000742 in 1,508,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: YAP1 NM_001130145.3 inframe_insertion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.156

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 Likely_benign. Variant got -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001130145.3.
• BS2: High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAP1	NM_001130145.3	c.115_144dup	p.Ala39_Pro48dup	inframe_insertion	1/9	ENST00000282441.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YAP1	ENST00000282441.10	c.115_144dup	p.Ala39_Pro48dup	inframe_insertion	1/9	1	NM_001130145.3	P2

Frequencies

GnomAD3 genomes AF: 0.0000660 AC: 10 AN: 151538 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000476

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000752 AC: 102 AN: 1357282 Hom.: 0 Cov.: 31 AF XY: 0.0000568 AC XY: 38 AN XY: 669182

Gnomad4 AFR exome AF: 0.0000735

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: 0.000106

Gnomad4 NFE exome AF: 0.0000875

Gnomad4 OTH exome AF: 0.0000358

GnomAD4 genome AF: 0.0000660 AC: 10 AN: 151538 Hom.: 0 Cov.: 32 AF XY: 0.0000811 AC XY: 6 AN XY: 74020

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000476

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

research

Gharavi Laboratory, Columbia University

Sep 16, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1479331868; hg19: chr11-101981686;