rs990765765

Variant names:

• chr11-102110910-C-G
• NM_001130145.3:c.62C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-102110910-C-G
• chr11-102110910-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130145.3(YAP1):​c.62C>G​(p.Ser21Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000078 in 1,281,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S21L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: YAP1 NM_001130145.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1409199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAP1	NM_001130145.3	c.62C>G	p.Ser21Trp	missense_variant	Exon 1 of 9	ENST00000282441.10	NP_001123617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAP1	ENST00000282441.10	c.62C>G	p.Ser21Trp	missense_variant	Exon 1 of 9	1	NM_001130145.3	ENSP00000282441.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.80e-7 AC: 1 AN: 1281464 Hom.: 0 Cov.: 31 AF XY: 0.00000158 AC XY: 1 AN XY: 631080

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	.;T;.;.;.;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.82	T;T;T;T;T;T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N;N;N;N;N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.73	N;N;N;N;.;.;N
REVEL	Benign	0.081
Sift	Pathogenic	0.0	D;D;D;D;.;.;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D;D
Polyphen		0.73, 0.82	.;P;.;.;.;P;P
Vest4		0.22
MutPred		0.23		Loss of phosphorylation at S21 (P = 0.005);Loss of phosphorylation at S21 (P = 0.005);Loss of phosphorylation at S21 (P = 0.005);Loss of phosphorylation at S21 (P = 0.005);Loss of phosphorylation at S21 (P = 0.005);Loss of phosphorylation at S21 (P = 0.005);Loss of phosphorylation at S21 (P = 0.005);
MVP		0.10
MPC		1.6
ClinPred		0.42	T
GERP RS		2.4
Varity_R		0.29
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.

Other links and lift over

hg19: chr11-101981641;