19-10113847-C-T

Position:

chr19-10113847-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001198690.2(PPAN-P2RY11):c.1556C>T(p.Ala519Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,612,872 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 26 hom. )

Consequence

PPAN-P2RY11
NM_001198690.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.55

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:

P2RY11 (HGNC:):

P2RY11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002979964).

BP6

Variant 19-10113847-C-T is Benign according to our data. Variant chr19-10113847-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY11	NM_002566.5 linkuse as main transcript	c.234C>T	p.Cys78Cys	synonymous_variant	2/2	ENST00000321826.5	NP_002557.2	Q96G91
PPAN-P2RY11	NM_001198690.2 linkuse as main transcript	c.1556C>T	p.Ala519Val	missense_variant	13/13		NP_001185619.1	A0A0A6YYI3
PPAN-P2RY11	NM_001040664.3 linkuse as main transcript	c.1494C>T	p.Cys498Cys	synonymous_variant	13/13		NP_001035754.1	Q9NQ55A0A0B4J1V8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
P2RY11	ENST00000321826.5 linkuse as main transcript	c.234C>T	p.Cys78Cys	synonymous_variant	2/2	1	NM_002566.5	ENSP00000323872.4	Q96G91
PPAN-P2RY11	ENST00000393796.4 linkuse as main transcript	c.1494C>T	p.Cys498Cys	synonymous_variant	13/13	1		ENSP00000377385.4	A0A0B4J1V8
PPAN-P2RY11	ENST00000428358.5 linkuse as main transcript	c.1556C>T	p.Ala519Val	missense_variant	13/13	2		ENSP00000411918.1	A0A0A6YYI3
P2RY11	ENST00000471843.1 linkuse as main transcript	n.*13C>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

465

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00481

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00346

AC:

851

AN:

246188

Hom.:

AF XY:

0.00345

AC XY:

461

AN XY:

133540

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00530

Gnomad OTH exome

AF:

0.00480

GnomAD4 exome

AF:

0.00264

AC:

3856

AN:

1460582

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

1969

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.00277

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00305

AC:

465

AN:

152290

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

244

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.00481

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.00196

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00388

AC:

471

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00219

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	P2RY11: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.024

DANN

Uncertain

0.98

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.26

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.030

REVEL

Benign

0.025

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.10

MVP

0.030

ClinPred

0.022

GERP RS

-8.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over