chr11-102110859-G-C

Variant names:

• chr11-102110859-G-C
• rs867829919
• NM_001130145.3:c.11G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130145.3(YAP1):​c.11G>C​(p.Gly4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,261,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G4E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: YAP1 NM_001130145.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.249
• Publications: 1 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043026358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAP1	NM_001130145.3	MANE Select	c.11G>C	p.Gly4Ala	missense	Exon 1 of 9	NP_001123617.1	P46937-1
	YAP1	NM_001282101.2		c.11G>C	p.Gly4Ala	missense	Exon 1 of 9	NP_001269030.1	P46937-9
	YAP1	NM_001282100.2		c.11G>C	p.Gly4Ala	missense	Exon 1 of 8	NP_001269029.1	P46937-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAP1	ENST00000282441.10	TSL:1 MANE Select	c.11G>C	p.Gly4Ala	missense	Exon 1 of 9	ENSP00000282441.5	P46937-1
	YAP1	ENST00000531439.5	TSL:1	c.11G>C	p.Gly4Ala	missense	Exon 1 of 8	ENSP00000431574.1	P46937-2
	YAP1	ENST00000951261.1		c.11G>C	p.Gly4Ala	missense	Exon 1 of 10	ENSP00000621320.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1261776 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 621494

African (AFR) AF: 0.00 AC: 0 AN: 25400

American (AMR) AF: 0.00 AC: 0 AN: 22240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20888

East Asian (EAS) AF: 0.00 AC: 0 AN: 25782

South Asian (SAS) AF: 0.00 AC: 0 AN: 64680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1014740

Other (OTH) AF: 0.0000196 AC: 1 AN: 51026

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.25
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.17		Gain of glycosylation at P7 (P = 0.1525)
MVP		0.068
MPC		1.3
ClinPred		0.15	T
GERP RS		-0.10
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.16
gMVP		0.15
Mutation Taster		=85/15	polymorphism

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: rs867829919; hg19: chr11-101981590;