19-10114109-A-G

Position:

chr19-10114109-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002566.5(P2RY11):c.496A>G(p.Ser166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 1,600,876 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00028 ( 5 hom. )

Consequence

P2RY11
NM_002566.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.82

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009763926).

BP6

Variant 19-10114109-A-G is Benign according to our data. Variant chr19-10114109-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3044892.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY11	NM_002566.5 link	c.496A>G	p.Ser166Gly	missense_variant	2/2	ENST00000321826.5	NP_002557.2	Q96G91
PPAN-P2RY11	NM_001040664.3 link	c.1756A>G	p.Ser586Gly	missense_variant	13/13		NP_001035754.1	Q9NQ55A0A0B4J1V8
PPAN-P2RY11	NM_001198690.2 link	c.*255A>G		3_prime_UTR_variant	13/13		NP_001185619.1	A0A0A6YYI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
P2RY11	ENST00000321826.5 link	c.496A>G	p.Ser166Gly	missense_variant	2/2	1	NM_002566.5	ENSP00000323872.4	Q96G91
PPAN-P2RY11	ENST00000393796.4 link	c.1756A>G	p.Ser586Gly	missense_variant	13/13	1		ENSP00000377385.4	A0A0B4J1V8
PPAN-P2RY11	ENST00000428358.5 link	c.*255A>G		3_prime_UTR_variant	13/13	2		ENSP00000411918.1	A0A0A6YYI3

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000573

AC:

134

AN:

233966

Hom.:

AF XY:

0.000476

AC XY:

AN XY:

128180

show subpopulations

Gnomad AFR exome

AF:

0.00799

Gnomad AMR exome

AF:

0.000175

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:

0.0000374

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000275

AC:

399

AN:

1448604

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

181

AN XY:

721282

show subpopulations

Gnomad4 AFR exome

AF:

0.00926

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.000680

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152272

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00794

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000575

Hom.:

Bravo

AF:

0.00241

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000671

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

P2RY11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 07, 2020

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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.11

DANN

Benign

0.93

DEOGEN2

Benign

0.059

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.53

.;N

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.071

Sift

Benign

0.24

T;T

Sift4G

Uncertain

0.033

D;T

Polyphen

0.0020

.;B

Vest4

0.074

MVP

0.19

MPC

0.050

ClinPred

0.0067

GERP RS

0.34

Varity_R

0.099

gMVP

0.22

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