19-10113805-C-A

Variant names:

• chr19-10113805-C-A
• rs767138158
• NM_002566.5:c.192C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198690.2(PPAN-P2RY11):​c.1514C>A​(p.Pro505Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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. P505L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPAN-P2RY11 NM_001198690.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 2 publications found

Genes affected

P2RY11 (HGNC:8540): (purinergic receptor P2Y11) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is coupled to the stimulation of the phosphoinositide and adenylyl cyclase pathways and behaves as a selective purinoceptor. Naturally occuring read-through transcripts, resulting from intergenic splicing between this gene and an immediately upstream gene (PPAN, encoding peter pan homolog), have been found. The PPAN-P2RY11 read-through mRNA is ubiquitously expressed and encodes a fusion protein that shares identity with each individual gene product. [provided by RefSeq, Jul 2008]

PPAN-P2RY11 (HGNC:33526): (PPAN-P2RY11 readthrough) This locus represents naturally occurring read-through transcription between the adjacent PPAN and P2RY11 genes. Alternative splicing results in two transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. This transcript is found to be ubiquitously expressed and is up-regulated by agents inducing granulocytic differentiation. However, its functional significance in vivo remains unclear. [provided by RefSeq, Nov 2010]

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=0.07165435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198690.2. 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
	P2RY11	NM_002566.5	MANE Select	c.192C>A	p.Ala64Ala	synonymous	Exon 2 of 2	NP_002557.2
	PPAN-P2RY11	NM_001198690.2		c.1514C>A	p.Pro505Gln	missense	Exon 13 of 13	NP_001185619.1	A0A0A6YYI3
	PPAN-P2RY11	NM_001040664.3		c.1452C>A	p.Ala484Ala	synonymous	Exon 13 of 13	NP_001035754.1	A0A0B4J1V8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY11	ENST00000321826.5	TSL:1 MANE Select	c.192C>A	p.Ala64Ala	synonymous	Exon 2 of 2	ENSP00000323872.4	Q96G91
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1452C>A	p.Ala484Ala	synonymous	Exon 13 of 13	ENSP00000377385.4	A0A0B4J1V8
	PPAN-P2RY11	ENST00000428358.5	TSL:2	c.1514C>A	p.Pro505Gln	missense	Exon 13 of 13	ENSP00000411918.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.015
DANN	Benign	0.75
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.97	T
PhyloP100		-2.8
PROVEAN	Benign	0.23	N
REVEL	Benign	0.061
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.089	T
Vest4		0.22
MutPred		0.16		Loss of catalytic residue at P504 (P = 0.016)
MVP		0.030
ClinPred		0.21	T
GERP RS		-8.0
Mutation Taster		=99/1	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: rs767138158; hg19: chr19-10224481; COSMIC: COSV99461942; COSMIC: COSV99461942;