chr19-10113754-C-A

Position:

chr19-10113754-C-A

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.1463C>A(p.Ala488Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 1,614,076 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 6 hom. )

Consequence

PPAN-P2RY11
NM_001198690.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.11

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=0.0034784079).

BP6

Variant 19-10113754-C-A is Benign according to our data. Variant chr19-10113754-C-A is described in ClinVar as [Benign]. Clinvar id is 777414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-10113754-C-A is described in Lovd as [Likely_benign].

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.141C>A	p.Gly47Gly	synonymous_variant	2/2	ENST00000321826.5	NP_002557.2	Q96G91
PPAN-P2RY11	NM_001198690.2 linkuse as main transcript	c.1463C>A	p.Ala488Asp	missense_variant	13/13		NP_001185619.1	A0A0A6YYI3
PPAN-P2RY11	NM_001040664.3 linkuse as main transcript	c.1401C>A	p.Gly467Gly	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.141C>A	p.Gly47Gly	synonymous_variant	2/2	1	NM_002566.5	ENSP00000323872.4	Q96G91
PPAN-P2RY11	ENST00000393796.4 linkuse as main transcript	c.1401C>A	p.Gly467Gly	synonymous_variant	13/13	1		ENSP00000377385.4	A0A0B4J1V8
PPAN-P2RY11	ENST00000428358.5 linkuse as main transcript	c.1463C>A	p.Ala488Asp	missense_variant	13/13	2		ENSP00000411918.1	A0A0A6YYI3
P2RY11	ENST00000471843.1 linkuse as main transcript	n.474C>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

486

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000836

AC:

208

AN:

248838

Hom.:

AF XY:

0.000564

AC XY:

AN XY:

134756

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000539

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000323

AC:

472

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000272

AC XY:

198

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00319

AC:

486

AN:

152258

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000741

Hom.:

Bravo

AF:

0.00363

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000980

AC:

119

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PPAN-P2RY11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.39

DANN

Uncertain

0.98

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.20

REVEL

Benign

0.035

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.38

MVP

0.11

ClinPred

0.012

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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