Genetic Variant P2RY11:p.Gly47Gly (chr19-10113754-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001198690.2(PPAN-P2RY11):c.1463C>T(p.Ala488Val) 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. 13/18 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. A488D) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

PPAN-P2RY11
NM_001198690.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

1 publications found

Variant links:

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]

P2RY11 links:

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]

PPAN-P2RY11 links:

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ACMG classification

Classification was made for transcript

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=0.05120617).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RY11	NM_002566.5	MANE Select	c.141C>T	p.Gly47Gly	synonymous	Exon 2 of 2	NP_002557.2
PPAN-P2RY11	NM_001198690.2		c.1463C>T	p.Ala488Val	missense	Exon 13 of 13	NP_001185619.1	A0A0A6YYI3
PPAN-P2RY11	NM_001040664.3		c.1401C>T	p.Gly467Gly	synonymous	Exon 13 of 13	NP_001035754.1	A0A0B4J1V8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RY11	ENST00000321826.5	TSL:1 MANE Select	c.141C>T	p.Gly47Gly	synonymous	Exon 2 of 2	ENSP00000323872.4	Q96G91
PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1401C>T	p.Gly467Gly	synonymous	Exon 13 of 13	ENSP00000377385.4	A0A0B4J1V8
PPAN-P2RY11	ENST00000428358.5	TSL:2	c.1463C>T	p.Ala488Val	missense	Exon 13 of 13	ENSP00000411918.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248838

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.57

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.26

M_CAP

Benign

0.0035

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

PhyloP100

-1.1

PROVEAN

Benign

0.010

REVEL

Benign

0.013

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.15

MutPred

0.23

Loss of disorder (P = 0.059)

MVP

0.040

ClinPred

0.077

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over