rs990765765

Variant names:

• chr11-102110910-C-G
• rs990765765
• 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. The variant received 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
• Publications: 0 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, Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

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.62C>G	p.Ser21Trp	missense	Exon 1 of 9	NP_001123617.1	P46937-1
	YAP1	NM_001282101.2		c.62C>G	p.Ser21Trp	missense	Exon 1 of 9	NP_001269030.1	P46937-9
	YAP1	NM_001282100.2		c.62C>G	p.Ser21Trp	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.62C>G	p.Ser21Trp	missense	Exon 1 of 9	ENSP00000282441.5	P46937-1
	YAP1	ENST00000531439.5	TSL:1	c.62C>G	p.Ser21Trp	missense	Exon 1 of 8	ENSP00000431574.1	P46937-2
	YAP1	ENST00000951261.1		c.62C>G	p.Ser21Trp	missense	Exon 1 of 10	ENSP00000621320.1

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

African (AFR) AF: 0.00 AC: 0 AN: 25156

American (AMR) AF: 0.00 AC: 0 AN: 19624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20806

East Asian (EAS) AF: 0.00 AC: 0 AN: 26870

South Asian (SAS) AF: 0.00 AC: 0 AN: 64988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42454

Middle Eastern (MID) AF: 0.000274 AC: 1 AN: 3654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1025878

Other (OTH) AF: 0.00 AC: 0 AN: 52034

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.081
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.019	D
Polyphen		0.73	P
Vest4		0.22
MutPred		0.23		Loss of phosphorylation at S21 (P = 0.005)
MVP		0.10
MPC		1.6
ClinPred		0.42	T
GERP RS		2.4
PromoterAI		0.027	Neutral
Varity_R		0.29
gMVP		0.13
Mutation Taster		=71/29	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: rs990765765; hg19: chr11-101981641;