19-10114261-G-A

Position:

• chr19-10114261-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002566.5(P2RY11):​c.648G>A​(p.Leu216Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,598,512 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (10 hom., cov: 34)
  • Exomes 𝑓: 0.0015 (17 hom.)
• Consequence: P2RY11 NM_002566.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.660

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 19-10114261-G-A is Benign according to our data. Variant chr19-10114261-G-A is described in ClinVar as [Benign]. Clinvar id is 777415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0081 (1234/152350) while in subpopulation AFR AF= 0.0248 (1033/41582). AF 95% confidence interval is 0.0236. There are 10 homozygotes in gnomad4. There are 613 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY11	NM_002566.5	c.648G>A	p.Leu216Leu	synonymous_variant	2/2	ENST00000321826.5	NP_002557.2
PPAN-P2RY11	NM_001040664.3	c.1908G>A	p.Leu636Leu	synonymous_variant	13/13		NP_001035754.1
PPAN-P2RY11	NM_001198690.2	c.*407G>A		3_prime_UTR_variant	13/13		NP_001185619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY11	ENST00000321826.5	c.648G>A	p.Leu216Leu	synonymous_variant	2/2	1	NM_002566.5	ENSP00000323872.4
PPAN-P2RY11	ENST00000393796.4	c.1908G>A	p.Leu636Leu	synonymous_variant	13/13	1		ENSP00000377385.4
PPAN-P2RY11	ENST00000428358.5	c.*407G>A		3_prime_UTR_variant	13/13	2		ENSP00000411918.1

Frequencies

GnomAD3 genomes AF: 0.00805 AC: 1226 AN: 152232 Hom.: 10 Cov.: 34

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00719

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00297 AC: 674 AN: 226894 Hom.: 6 AF XY: 0.00264 AC XY: 330 AN XY: 125216

Gnomad AFR exome AF: 0.0254

Gnomad AMR exome AF: 0.00412

Gnomad ASJ exome AF: 0.00354

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000659

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.00207

GnomAD4 exome AF: 0.00146 AC: 2110 AN: 1446162 Hom.: 17 Cov.: 35 AF XY: 0.00144 AC XY: 1038 AN XY: 719802

Gnomad4 AFR exome AF: 0.0251

Gnomad4 AMR exome AF: 0.00408

Gnomad4 ASJ exome AF: 0.00368

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000655

Gnomad4 OTH exome AF: 0.00361

GnomAD4 genome AF: 0.00810 AC: 1234 AN: 152350 Hom.: 10 Cov.: 34 AF XY: 0.00823 AC XY: 613 AN XY: 74502

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.00718

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00499 Hom.: 3

Bravo AF: 0.00897

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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_noAF	Benign	-0.59
CADD	Benign	3.3
DANN	Benign	0.79
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

Other links and lift over

dbSNP: rs115986278; hg19: chr19-10224937;